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0FF1.jpg|Fig. I.1 Macule.
 Congenital white macule of nevus de

pigmentosus on thigh.
0FF2.jpg|Fig. I.2 Papules on the trunk of a patient with lichen n
itidus.
0FF3.jpg|Fig. I.3 Plaques with silvery scale in severe psoriasis.

0FF4.jpg|Fig. I.4 Nodules on the forehead of a woman with lymphom
a.
0FF5.jpg|Fig. I.5 Vesicles and bullae in a child with severe chic
kenpox.
0FF6.jpg|Fig. I.6 Pustules in a patient with inflammatory acne.
0FF7.jpg|Fig. I.7 Annular plaques on the neck of a patient with sarc
oidosis.
0FF8.jpg|Fig. I.8 Leonine facies in a patient with mycosis fungoides
.
0FF9.jpg|Fig. I.9 Linear papules representing the Koebner phenomenon
in lichen planus.
0FF10.jpg|Fig. I.10 Poikiloderma in a patient with mycosis fungoides
.
0FF11.jpg|Fig. I.11 Reticulated erythema of the extremities of a pat
ient with Fifth disease.
0FF12.jpg|Fig. I.12 Black eschar in a patient with invasive Rhizo
pus infection.
0FF13.jpg|Fig. I.13 Bluish discoloration of the face of a patient ta
king amiodarone.
0FF14.jpg|Fig. I.14 Brown macules of benign penile lentiginosis.
0FF15.jpg|Fig. I.15 Greenish exudate in a Pseudomonas-infecte
d ulcer on a patient who was hospitalized after falling asleep inebriated upon a
fire ant hill.
0FF16.jpg|Fig. I.16 Grey macules on the trunk in erythema dyschromic
um perstans (ashy dermatosis).
0FF17.jpg|Fig. I.17 Grey discoloration in argyria.
0FF18.jpg|Fig. I.18 Grey discoloration due to oral treatment with qu
inacrine, an antimalarial.
0FF19.jpg|Fig. I.19 Salmon-red patches in pityriasis rubra pilaris.
Note follicular papules and islands of sparing.
0FF20.jpg|Fig. I.20 Purplish (violaceous) plaques in lichen planus.
0FF21.jpg|Fig. I.21 White plaques, representing scarring in discoid
lupus erythematosus.
0FF22.jpg|Fig. I.22 Yellow xanthomas in a patient with Alagille synd
rome.
0FF23.jpg|Fig. I.23 Important pathologic patterns of inflammation
in the skin (adapted from reference 21). A Superficial perivascular
dermatitis. B Superficial and deep perivascular dermatitis. C Inte
rface dermatitis, vacuolar type. D Interface dermatitis, lichenoid type.
E Nodular dermatitis. F Diffuse dermatitis. G Interstitial
dermatitis. H Folliculitis. I Intraepidermal vesicular dermatitis.
J Subepidermal vesicular dermatitis. K Septal panniculitis. L Lobular panniculitis.
0FT1.jpg|Table I.1 Approach to the dermatology problem patient.
0FT2.jpg|Table I.2 Differential diagnosis categories.
0FT3.jpg|Table I.3 Cutaneous histopathologic findings.
0FT4.jpg|Table I.4 Major architectural patterns for inflammatory and
some neoplastic skin diseases.
0FT5.jpg|Table I.5 Simplified list of granulomatous diseases.
0FT6.jpg|Table I.6 Neoplasm staining generalization (idealized resul
ts do not hold true in every instance).
1FT1.jpg|Table 1.1 Basic science curriculum.
2FF1.jpg|Fig. 2.1 Normal skin: trunk. Note epidermal layers f
rom the surface: stratum corneum, stratum granulosum, stratum spinulosum and str
atum basale. Tightly packed dermal collagen occurs near the epidermal–derm
al junction, and more loosely arranged collagen is found deeper in the dermis. A
cluster of small blood vessels and nerves is seen in the dermis.
2FF2.jpg|Fig. 2.2 Normal skin: palm. Note that the epidermis
is thicker than seen in . The compact and thick stratum corneum is typical of sk
in of the palms and soles.
2FF3.jpg|Fig. 2.3 Normal melanocyte. A whole mount of epiderm
is has been stained for the presence of the enzyme tyrosinase, which typifies me
lanocytes. Note that the surrounding keratinocytes are virtually invisible. An a
djacent hair shaft passes through the specimen. Melanocytes contain long dendrit
ic processes that deliver protective melanosomes to nearby keratinocytes.
2FF4.jpg|Fig. 2.4 Epon-embedded section of human epidermis. N
ote the pale cytoplasm and extended dendritic process of a central Langerhans ce
ll (arrow), which resides above the basal cell layer of the epidermis.
2FF5.jpg|Fig. 2.5 Verruca vulgaris. Human papilloma virus inf
ection induces acanthosis, papillomatosis, and hypergranulosis of the epidermis.
Note that the overall outline of this tumor resembles the configuration of wart
s as seen in vivo.
2FF6.jpg|Fig. 2.6 Verruca vulgaris. Wart infections in humans
can affect virtually any cutaneous surface. Periungual infections, as seen in t
his photograph, are both common and difficult to treat.
2FF7.jpg|Fig. 2.7 Dermatophytosis. Periodic acid-Schiff (PAS)
staining for neutral mucopolysaccarides reveals branching eosinophilic fungal h
yphae within the stratum corneum in a patient with tinea corporis. In the absenc
e of diastase, glycogen within keratinocytes also stains with PAS.
2FF8.jpg|Fig. 2.8 Dermatophytosis. This clinical presentation
of tinea corporis typifies cutaneous dermatophyte infections.
2FF9.jpg|Fig. 2.9 Herpes zoster. Herpes zoster infection in a
young adult who is also infected with HIV.
2FF10.jpg|Fig. 2.10 Tzanck smear. A large, multinucleated ker
atinocyte is seen in a Tzanck smear from an HIV infected patient with herpes zos
ter.
2FF11.jpg|Fig. 2.11 Pemphigus vulgaris (immunofluorescence).
Intercellular staining of epidermal keratinocytes reveals the in vivo deposition
of antibodies to desmoglein III.
2FF12.jpg|Fig. 2.12 Melanoma. This thick melanoma has virtual
ly no associated inflammatory cells as determined by histopathology. The lack of
a host response indicates a poor prognosis for the patient.
2FF13.jpg|Fig. 2.13 Epidermolytic hyperkeratosis. Compact ort
hokeratosis overlies an epidermis showing granular and vacuolar change in its up
per layers.
2FF14.jpg|Fig. 2.14 Toxic epidermal necrolysis. Full thicknes
s epidermal cell death, with secondary bulla formation.
2FF15.jpg|Fig. 2.15 Toxic epidermal necrolysis. Full thicknes
s epidermal cell death leads to stripping off of the epidermis. In this African
patient, it becomes apparent that melanin is located predominantly in the epider
mis.
2FF16.jpg|Fig. 2.16 Albinism in an infant. Note the normally
pigmented fingers of the child's mother. Patients with albinism are at substanti
ally higher risk for ultraviolet carcinogenesis.
2FF17.jpg|Fig. 2.17 Thrombotic vasculopathy. Thrombosed blood
vessels with fibrin in vessel lumina in a patient with type I cryoglobulinemia
and multiple myeloma.
2FF18.jpg|Fig. 2.18 Thrombotic vasculopathy. Retiform purpura
with secondary bulla formation in a patient with type 1 cryoglobulinemia. The h
istologic findings are seen in .
2FF19.jpg|Fig. 2.19 Mr Frederick H Hemming and his fiancée,
Mary Anne Bloxam. Their portraits were painted in 1824–25 by the Engli
sh portraiture artist, Thomas Lawrence. The intrinsic ‘beauty’ of th
ese individuals allows one to examine their features with interest. Courtesy of
the Kimball Art Museum, Fort Worth, Texas.

2FF20.jpg|Fig. 2.20 Vitiligo. This African-American man has v
itiligo that affects distal portions of his fingers. Pigmentary disorders of thi
s sort are much more obvious in patients with substantial natural pigmentation.
2FF21.jpg|Fig. 2.21 Alopecia areata. The detrimental social i
mpact of hair loss in patients with diseases such as alopecia areata cannot be u
nderestimated.
2FT1.jpg|Table 2.1 Selected requirements and failings of skin.
2FT2.jpg|Table 2.2 Common autoimmune skin diseases.
2FT3.jpg|Table 2.3 Organizations and services that address needs of
patients with skin disease.
3FF1.jpg|Fig. 3.1 Critical events in the development of skin and
its specialized structures. The time-line indicates their time of initiation
defined by fetal age (EGA) and duration of pregnancy (LMP). Unless otherwise st
ated, times refer to back skin.
3FF2.jpg|Fig. 3.2 Development of the epidermis.
3FF3.jpg|Fig. 3.3 Development of the epidermis. A At 36 days'
EGA, the embryonal epidermis consists of only two layers, a superficial perider
m layer overlying a basal layer. B By 72 days, the periderm and basal lay
ers are separated by a well-defined intermediate layer, which is highly prolifer
ative and gives rise to numerous intermediate layers by the end of the second tr
imester. Keratinization occurs first in the appendageal structures (beginning of
second trimester) and then the newly stratified epidermis (end of second trimes
ter). C A distinct granular cell layer and stratum corneum are seen in ne
onatal skin. Hair follicle buds are first seen in the dermis of the face and sca
lp between 75 and 80 days. D An early bulbous hair peg-stage follicle fro
m a mid-second semester fetus. Photomicrographs courtesy of Dr Karen Holbrook, f
rom Eichenfield LF, Frieden IJ, Esterly NB (eds) Textbook of Neonatal Dermatolog
y. London: WB Saunders, 2001.
3FF4.jpg|Fig. 3.4 Nail development. The developing nail from
65 to 85 days' EGA, scanning electron and light microscopy. The nail field bound
aries are marked by folds seen clearly in A, B, and E. The lines d
elimited by arrows indicate the plane of the section taken for the accompanying
histologic sections. C, D & F show the increasing thickness and diffe
rentiation of the epidermis forming the presumptive nail plate. Reproduced with
permission from Schachner LA, Hansen RC (eds) Pediatric Dermatology, 2nd edn. Lo
ndon: Churchill Livingstone, 1995.
3FF5.jpg|Fig. 3.5 Sweat gland development. Plantar epidermis
from the digit of a late first-trimester human fetus showing a multilayered epid
ermis and the primary epidermal ridges (arrows) that will develop into sweat gla
nds and ducts. Reproduced with permission from Schachner LA, Hansen RC (eds) Ped
iatric Dermatology, 2nd edn. London: Churchill Livingstone, 1995.
3FT1.jpg|Table 3.1 Comparative features of premature, newborn, an
d adult skin32. Reproduced with permission from Schachner LA, Han
sen RC (eds) Pediatric Dermatology, 2nd edn. London: Churchill Livingstone,1995.
4FF1.jpg|Fig. 4.1 Tissue processing. The biopsy from the mela
noma tumor can be processed in four different ways, each with distinct advantage
s and disadvantages.
4FF2.jpg|Fig. 4.2 Laser capture microdissection. LCM is used
to selectively procure individual cells or clusters of cells from tissue section
s. A glass slide with a section of paraffin-embedded or cryopreserved tissue is
stained and placed on the microscope stage. A cap coated with a thermoplastic tr
ansfer membrane is placed directly over the tissue section. The operator identif
ies the cells of interest by looking through the eyepiece of the microscope or b
y looking at a monitor. A low-energy infrared laser is then pulsed that melts th
e transfer film on to the cells of interest. The cap is then lifted from the sec
tion to separate the selected cells from the remainder of the tissue section. Mo
lecules of interest, including DNA, RNA, and protein, can be extracted from the
microdissected cells present on the cap3 .
4FF3.jpg|Fig. 4.3 Polymerase chain reaction. A Each cycle con
tains the following steps: (1) Denaturation – separate the two strands of
DNA by heating to >90°C; (2) primer annealing or primer hybridization &
#8211; allow the oligonucleotide primers to bind to the template DNA by cooling
to 50–65°C; (3) primer extension – DNA polymerase catalyzes the
addition of nucleotides (A, G, C, T) that are complementary to the DNA template
, beginning with the primer and extending 3′ at the optimal temperature of
72°C; and (4) repeat the complete cycle 30–40 times. B Each c
ycle increases the number of PCR products twofold. The total number of PCR produ
cts after n cycles will be 2n times the original amount.
4FF4.jpg|Fig. 4.4 DNA sequencing. An oligonucleotide primer h
ybridizes to the DNA to be sequenced and DNA polymerase synthesizes a second com
plementary strand. The synthesis of the second strand is interrupted randomly by
the incorporation of the fluorescent nucleotide analogs (ddATP, ddGTP, ddCTP, d
dTTP), and the DNA fragments containing this final nucleotide analog can be iden
tified because each of the four ddNTPs is labeled with a different color fluoroc
hrome. Gel electrophoresis is used to separate the different sizes of DNA fragme
nts. The different length DNA strands terminating with different fluorochrome-la
beled nucleotide analogs pass a fluorescence detector and indicate the order of
the DNA sequence (see Table 4.2 for more details).
4FF5.jpg|Fig. 4.5 Reverse transcription-PCR. A Reverse transc
riptase can convert mRNA to cDNA in three different ways, depending on the prime
r used for the initial RT step: (1) Random hexamer primers; (2) oligo dT primers
; and (3) gene-specific primers (see Table 4.3 for more details). After the mRNA
has been converted to cDNA, primers that can hybridize to specific sequences ar
e added and PCR amplification is performed as described in Table 4.1. B R
eal-time PCR is able to precisely measure the amount of PCR product continuously
(y axis) after each cycle (x axis). Each plotted line represents
the amount of PCR product present in a different sample. In samples that initial
ly contain more mRNA gene transcripts, real-time PCR will demonstrate an exponen
tial increase in PCR product earlier after fewer PCR cycles.
4FF6.jpg|Fig. 4.6 Western blot technique. The solubilized pro
tein mix is separated on a polyacrylamide gel and transferred electrophoreticall
y to a membrane. The membrane is soaked in a buffer containing antibody. The bou
nd antibody is detected by a chromogenic or chemiluminescent assay.
4FF7.jpg|Fig. 4.7 Nucleic acid arrays. RNA molecules are reve
rse transcribed to generate cDNA probes (see Table 4.3) which are labeled with f
luorescent nucleotides. Probes are then hybridized to the oligonucleotide microa
rray(s). Usually, the patterns of gene expression of two samples are compared, s
uch as normal versus tumor or treated versus untreated. The two samples can be l
abeled with differently colored fluorescent probes and can be hybridized to the
same array simultaneously (see Table 4.5 for more details).
4FF8.jpg|Fig. 4.8 Bioinformatics. A goal of bioinformatics is
to give users access to huge amounts of biological information in a way that is
easy to use and analyze. One example is Entrez produced by the National Center
for Biotechnology Information, available at http://www.ncbi.nom.nih.gov. This re
trieval system allows the user to search the biomedical literature (PubMed), nuc
leotride sequence database (GenBank), protein sequence database, three-dimension
al macromolecular structures, complete genome assemblies and organisms in GenBan
k (taxonomy). As indicated by arrows, users may access information from a single
database and also integrated information from several NCBI databases.
4FF9.jpg|Fig. 4.9 Proteomics with mass spectroscopy. The firs
t step is to reduce the complexity of the mixture of cellular proteins or peptid
es to be analyzed. The two main methods to separate proteins/peptides from each
other are two-dimensional gel electrophoresis and/or liquid chromatography colum
ns. Mass spectrometry analysis is then performed by first ionizing the separated
proteins/peptides into positively charged ions using lasers. Based on the timeof-flight of the charged ion, mass spectrometry can measure, record, and print o
ut the mass/charge ratio of every peptide along with signal intensity.
4FF10.jpg|Fig. 4.10 Transgenic mouse. A transgene construct,
defined as the transgene and regulatory region (promoter/enhancer), is prepared
for injection. The transgene is microinjected into fertilized eggs (single cell
stage) and the transgene integrates into the genome, usually at a single site. T
hese injected eggs are then implanted into a recipient mother, who then gives bi
rth to a heterozygous ‘founder’ mouse. The founder mice are bred wit
h normal non-transgenic mice of the same strain, and then two heterozygous trans
genic mice are mated.
4FF11.jpg|Fig. 4.11 Knockout transgenic mice. A targeting vec
tor that contains some sequences of the gene to be targeted is created and intro
duced into cells. This targeting vector is able to hybridize selectively to one
of the endogenous alleles of a gene, and modifies or deletes the endogenous gene
so that no normal protein is produced. The ES cells containing the ‘knock
ed out’ gene are introduced into early mouse embryos, which are then impla
nted into recipient mothers. The progeny will be chimeric mice. These chimeric m
ice are then mated to normal mice. To obtain completely knocked out mice, two he
terozygous mice are mated.
4FF12.jpg|Fig. 4.12 Skin gene therapy. In the direct in vi
vo approach, the desired gene is introduced directly into the skin as shown,
either directly injected intradermally (A) or biolistically discharged i
nto the epidermis and dermis (B). Both viral and non-viral vectors can be
delivered to the skin using these in vivo approaches.
4FF13.jpg|Fig. 4.13 Skin gene therapy. In the ex vivo
approach, keratinocytes are removed from the donor and, during ex vivo cu
lture, the desired gene is efficiently introduced, usually with viral vectors. S
kin equivalents or raft cultures containing these genetically modified keratinoc
ytes (along with a dermal portion containing fibroblasts) are constructed and th
en grafted back on to the donor.
4FT1.jpg| Table 4.1 Polymerase chain reaction. *Hybridization
actually forms the basis of several techniques in molecular biology, as the two
strands can be DNA:DNA (PCR, Southern blotting), DNA:RNA (Northern blotting, in situ hybridization), or RNA:RNA.
4FT2.jpg| Table 4.2 DNA sequencing. *Gel electrophoresis is u
sed in many molecular biological techniques to separate DNA, RNA, or protein mol
ecules of differing sizes.
4FT3.jpg| Table 4.3 Reverse transcription-PCR (RT-PCR).
4FT4.jpg| Table 4.4 Western blot.
4FT5.jpg| Table 4.5 Nucleic acid arrays.
4FT6.jpg| Table 4.6 Proteomics with mass spectrometry.
4FT7.jpg| Table 4.7 Transgenic mice.
4FT8.jpg| Table 4.8 Knockout transgenic mice.
4FT9.jpg| Table 4.9 Skin gene therapy.
4FT10.jpg| Table 4.10 Viral vectors for skin gene therapy.
5FF1.jpg|Fig. 5.1 Electron microscopic picture of a Langerhans ce
ll. Arrows indicate the Birbeck granules, rod shaped organelles specific for
Langerhans cells. Courtesy of N Romani, Department of Dermatology, University I
nnsbruck.
5FF2.jpg|Fig. 5.2 Langerhans cells express MHC II molecules.
In a sheet preparation of murine epidermis numerous Langerhans cells can be visu
alized by staining using an antibody against MHC II molecules (Ia antigen). Note
the dendritic shape of Langerhans cells.
5FF3.jpg|Fig. 5.3 Ontogeny of Langerhans cells. CD34+ precurs
or cells can develop into Langerhans cells or a monocyte/macrophage phenotype wh
ich ultimately differentiates into non-Langerhans dendritic cells. The developme
nt and differentiation is critically dependent on the presence of particular cyt
okines. CLA, cutaneous lymphocyte-associated antigen; DC, dendritic cell; Flt3-L
, Flt-3 ligand; GM-CSF, granulocyte/macrophage colony-stimulating factor; IL-4,
interleukin-4; LC, Langerhans cell; M-CSF, macrophage colony-stimulating factor;
SCF, stem cell factor; TGFβ, transforming growth factor β; TNFα,
tumor necrosis factor α.
5FF4.jpg|Fig. 5.4 Types of antigen presentation. Antigens are
presented by antigen presenting cells to the T cell receptor of CD4+ or CD8+ T
cells in association with either MHC II or MHC I molecules. The diversity of the
T cell receptors is generated by gene rearrangement. For reasons of clarity, th
e simplified gene rearrangement of the α chain is shown only in the CD4+ T
cell, that of the β chain in the CD8+ T cell. aa, amino acids; β2&nbsp
;m, microglobulin. Adapted from Modlin RL. Lymphocytes. In: Freedberg IM, Eisen
AZ, Wolf K, et al. (eds) Fitzpatrick's Dermatology in General Medicine, volume 1
. New York: McGraw-Hill; 1999;32:400–5.
5FF5.jpg|Fig. 5.5 T cell receptor-mediated signal transduction. Activation of the T cell receptor by presentation of the appropriate antigen
by antigen presenting cells in association with MHC molecules induces a complex
signal transduction cascade. The T cell receptor-associated signal transduction
is primarily mediated by the CD3 complex and the ζ chain. Upon activation t
he cytoplasmic tails of these molecules become phosphorylated by protein kinases
(p56lck, p59fyn, ZAP70). This causes downstream signaling
which ultimately leads to transcriptional activation of particular genes. Addit
ional stimuli are provided by the signaling of costimulatory molecules (CD2, ICA
M-1, CD28).
5FF6.jpg|Fig. 5.6 Role of costimulatory molecules during T cell a
ctivation. Presentation of the antigen by antigen presenting cells to the T
cell receptor in association with MHC molecules delivers the first signal necess
ary for T cell activation. The second signal is provided by the interaction of c
ostimulatory molecules present on antigen presenting cells and T cells. An antig
en-specific response is only induced when signal 1 and signal 2 are provided. Pr
esentation of the antigen in absence of signal 2 does not lead to an antigen-spe
cific response but induces anergy and tolerance, respectively. APC, antigen pres
enting cell; CSM, costimulatory molecule; MHC, major histocompatibility complex;
TCR, T cell receptor.
5FF7.jpg|Fig. 5.7 Development of the Th1 and Th2 responses. T
h1 and Th2 cells can differentiate under the influence of cytokines which are se
creted by various bystander cells. Cytokines can act in a stimulatory and inhibi
tory fashion. Th1 cells are crucial for T cell-mediated immunity, while Th2 cell
s support the development of humoral immunity. DC, dendritic cell; MC, mast cell
; Mph, macrophage; PC, plasma cell; IL, interleukin; IFNγ, interferon &#947
;. Adapted from Modlin RL. Lymphocytes. In: Freedberg IM, Eisen AZ, Wolf K, et a
l. (eds) Fitzpatrick's Dermatology in General Medicine, volume 1. New York: McGr
aw-Hill; 1999;32:400–5.
5FF8.jpg|Fig. 5.8 Structure of a prototype immunoglobulin. Th
e basic immunoglobulin structure consists of two identical light polypeptide cha
ins and two identical heavy polypeptide chains which are linked together by disu
lfide bonds. The antigen-binding site is at the N-terminal end.
5FF9.jpg|Fig. 5.9 T cell-dependent B cell activation. B cells
present the antigen in association with MHC II molecules to CD4+ T cells. This
results in the upregulation of CD154/CD40 ligand which interacts with CD40 expre
ssed on B cells. CD40-CD40 ligand interaction causes isotype switching of immuno
globulins and upregulation of CD80/86 which interacts with CD28 expressed on T c
ells. This results in further activation of T cells. Ag, antigen; CD40L, CD40 li
gand; Ig, immunoglobulin; MHC II, major histocompatibility complex II.
5FF10.jpg|Fig. 5.10 Induction of contact hypersensitivity. Ap
plication of contact allergens (Ag) induces the release of cytokines by keratino
cytes, Langerhans cells and other cells within the skin. These cytokines in turn
activate Langerhans cells which uptake the antigen and emigrate into the region
al lymph nodes. During this process, the Langerhans cells mature into dendritic
cells. In addition, the antigen is processed, re-expressed on the surface and fi
nally presented to naïve T cells in the regional lymph node. Upon appropria
te antigen presentation, T cells bearing the appropriate T cell receptor clonall
y expand and become effector T cells. These alter their migratory behaviour due
to the expression of specific surface molecules like CLA. Effector T cells recir
culate into the periphery where they may later meet the antigen again. Ag, antig
en; KC, keratinocyte.
5FF11.jpg|Fig. 5.11 Elicitation of contact hypersensitivity.
Application of contact allergens (Ag) into a sensitized individual causes the re

lease of cytokines by keratinocytes and Langerhans cells. These cytokines induce
the expression of adhesion molecules and activation of endothelial cells which
ultimately attracts leukocytes to the site of antigen application. Among these c
ells, T effector cells are present which are now activated upon antigen presenta
tion either by resident cells or by infiltrating Langerhans cells. Antigen-speci
fic T cell activation again induces the release of cytokines by T cells. This ca
uses the attraction of other inflammatory cells including granulocytes and macro
phages which ultimately cause the clinical manifestation of contact dermatitis.
Ag, antigen; DDC, dermal dendritic cell; KC, keratinocyte; CLA, cutaneous lympho
cyte antigen.
5FT1.jpg|Table 5.1 Phenotypic markers of resident versus activate
d human Langerhans cells.
5FT2.jpg|Table 5.2 Costimulatory molecules and their ligands*.
6FF1.jpg|Fig. 6.1 Typical cutaneous nerve and activation of nocic
eptor C neurons. There are two categories of axons: primary afferents A&#946
;, Aδ, and C (cell bodies in dorsal root ganglion), and sympathetic postgan
glionic fibers (cell bodies in sympathetic ganglion). A In primary (direc
t) activation of nociceptor C neurons, cell damage by stimulus induces lower pH,
potassium release, and synthesis of prostaglandins (the latter increasing sensi
tivity of neuron terminals to a number of substances). B In secondary act
ivation, impulses generated in the stimulated terminal propagate not only to the
spinal cord but also to other terminal branches, where they induce release of s
ubstance P. C Substance P activates mast cells via neurokinin 1 (NK-1) re
ceptors. Mast cells release histamine, which causes pruritus via neuronal H
1 receptors as well as tumor necrosis factor-α (TNF-α), and tryp
tase. D TNF-α augments activated nociceptor C neurons, and tryptase,
by its action on C fiber terminal proteinase-activated receptor-2 (PAR-2), caus
es release of additional substance P. (Upper part and part A adapted from Fields
HL, Martin JB. Pain. In: Braunwald E, Fauci AS, Kasper D, Hauser S, Longo D, Ja
meson J, eds. Harrison's Principles of Internal Medicine, 15th edition. N
ew York: McGraw Hill; 2001.)
6FT1.jpg|Table 6.1 Primary afferent neurons that innervate the sk
in.
6FT2.jpg|Table 6.2 Mediators of pruritus: relative potencies with
regard to pruritus, pain, vasodilation, and vasopermeability.
6FT3.jpg|Table 6.3 Examples of systemic drugs advocated for speci
fic antipruritic indications. (5-HT, 5-hydroxytryptamine)
6FT4.jpg|Table 6.4 Classification of antihistamines.
7FF1.jpg|Fig. 7.1 Insect bites. ‘Breakfast, lunch, and
dinner’ pruritic papules.
7FF2.jpg|Fig. 7.2 Connections and pathways between the causes and
manifestations of itching. Both underlying systemic and specific dermatolog
ic diseases can present with non-specific cutaneous changes or none at all, and
a cutaneous change that is not diagnostic at one time may be diagnostic later on
. Reproduced with permission from: Bernhard JD. Itch: mechanisms and management
of pruritus. ©1994 McGraw-Hill, Inc.
7FF3.jpg|Fig. 7.3 Lichen simplex chronicus on the neck of a man. Note the increased skin markings.
7FF4.jpg|Fig. 7.4 Extreme xerosis associated with pruritus in an
HIV-infected patient.
7FF5.jpg|Fig. 7.5 Atopic dermatitis with multiple lesions of prur
igo simplex and prurigo nodularis.
7FF6.jpg|Fig. 7.6 Atopic dermatitis. Multiple linear excoriat
ions are seen on the legs.
7FF7.jpg|Fig. 7.7 Multiple lesions of prurigo nodularis. Note
the sparing of the mid upper back (butterfly sign).
7FF8.jpg|Fig. 7.8 Xerosis and pruritus in a patient with chronic
renal failure on hemodialysis. There are a few papules of acquired perforati
ng dermatosis admixed with the scratch marks.

7FF9.jpg|Fig. 7.9 Brachioradial (solar) pruritus. The affecte
d area is outlined by ink.
7FF10.jpg|Fig. 7.10 Reflex sympathetic dystrophy with scaling and
erosion of the finger tips. Courtesy of Kalman Watzky, M.D.
7FF11.jpg|Fig. 7.11 Trigeminal trophic syndrome. Erosions and
ulcerations with hemorrhagic crusts favor the ala nasi (A, B). Obvious l
inear excoriations are seen in the second patient (B). Courtesy of Kalman
Watzky, M.D.
7FT1.jpg|Table 7.1 Descriptive and historical features of pruritu
s.
7FT2.jpg|Table 7.2 Possible laboratory studies in the evaluation
of pruritus. These laboratory tests should be performed according to the pat
ient’s history, in particular in cases of generalized pruritus of unknown
etiology.
7FT3.jpg|Table 7.3 Dermatologic diseases with pruritus. DH, d
ermatitis herpetiformis; BP, bullous pemphigoid.
7FT4.jpg|Table 7.4 Categories of pruritus therapy.
7FT5.jpg|Table 7.5 Differential diagnosis of pruritus or pricklin
g sensations provoked by water contact. Evident: cutaneous pathology may be
visible on physical exam or skin biopsy examination; Absent: cutaneous pathology
not seen on physical exam or skin biopsy examination. A cutaneous sarcoidosis m
ay be present.
7FT6.jpg|Table 7.6 Therapeutic options for renal pruritus.
7FT7.jpg|Table 7.7 Treatment options for hepatic or cholestatic p
ruritus.
7FT8.jpg|Table 7.8 Common pharmacologic etiologies of pruritus.
7FT9.jpg|Table 7.9 Idiopathic anal pain syndromes.
7FT10.jpg|Table 7.10 The stages of reflex sympathetic dystrophy.
7FT11.jpg|Table 7.11 Treatment options for reflex sympathetic dys
trophy. 1, prospective controlled trial; 2, retrospective trial or large cas
e study or series; 3, individual case reports or anecdotal.
7FT12.jpg|Table 7.12 Possible indications for topical capsaicin t
herapy.
8FF1.jpg|Fig. 8.1 Common psychopathologies underlying psychoderma
tologic disorders. Reprinted with permission from Wolverton: Comprehensive D
ermatologic Drug Therapy, W.B. Saunders, 2001.
8FF2.jpg|Fig. 8.2 Classification of psychodermatologic disorders. Adapted with permission from Wolverton: Comprehensive Dermatologic Drug The
rapy, W.B. Saunders, 2001.
8FF3.jpg|Fig. 8.3 Delusions of parasitosis. Samples of allege
d ‘parasites’ brought in by a patient (‘matchbox sign’).
8FF4.jpg|Fig. 8.4 Dermatitis artefacta. ‘Bizarre’
and unnatural appearance of the skin with angulated borders, possibly created w
ith a sharp instrument.
8FF5.jpg|Fig. 8.5 Scars from cigarette burns. Courtesy of Ron
Rapini, MD.
8FF6.jpg|Fig. 8.6 Neurotic excoriations. This patient continu
ed to pick at any blemish he could find on his arm.
8FF7.jpg|Fig. 8.7 Acne excoriée. This patient compulsive
ly picked at his acne lesions. Courtesy of Richard Odom, MD.
8FF8.jpg|Fig. 8.8 Prurigo nodularis. Courtesy of Ron Rapini,
MD.
8FF9.jpg|Fig. 8.9 Lichen simplex chronicus. Courtesy of Ron R
apini, MD.
8FF10.jpg|Fig. 8.10 Trichotillomania. Classic findings with s
mall areas of sparing.
8FF11.jpg|Fig. 8.11 Trichotillomania. Pigmented follicular ca
st. Courtesy of Ron Rapini, MD.

8FT1.jpg|Table 8.1 Signs and symptoms of monosymptomatic hypochon
driac psychosis. Reprinted with permission from Wolverton: Comprehensive Der
matologic Drug Therapy, W.B. Saunders, 2001
8FT2.jpg|Table 8.2 Signs and symptoms of obsessive-compulsive dis
order (OCD). Reprinted with permission from Wolverton: Comprehensive Dermato
logic Drug Therapy, W.B. Saunders, 2001
8FT3.jpg|Table 8.3 Signs and symptoms of generalized anxiety diso
rder (GAD). Reprinted with permission from Wolverton: Comprehensive Dermatol
ogic Drug Therapy, W.B. Saunders, 2001
8FT4.jpg|Table 8.4 Signs and symptoms of major depression. Re
printed with permission from Wolverton: Comprehensive Dermatologic Drug Therapy,
W.B. Saunders, 2001
9FF1.jpg|Fig. 9.1 Psoriatic plaque. Note the sharp demarcatio
n and silvery scale.
9FF2.jpg|Fig. 9.2 Symmetrical distribution of psoriatic plaques.
9FF3.jpg|Fig. 9.3 Widespread chronic plaque psoriasis.
9FF4.jpg|Fig. 9.4 Plantar psoriasis. A Erythematous scaling p
laques of the plantar surface. B Hyperkeratosis with minimal erythema.
9FF5.jpg|Fig. 9.5 Psoriasis of the genitalia. Erythematous pl
aques with scale on the penis and scrotum.
9FF6.jpg|Fig. 9.6 Guttate psoriasis. A Small discrete papules
and plaques of guttate psoriasis in an adolescent; note the Koebner phenomenon.
B Numerous papules due to the Koebner phenomenon after sunburn. B
, Courtesy of Ronald Rapini M.D.
9FF7.jpg|Fig. 9.7 Generalized pustular psoriasis. Large areas
of erythema with numerous pustules and the formation of lakes of pus.
9FF8.jpg|Fig. 9.8 Annular pustular psoriasis. As the annular
inflammatory plaques studded with pustules enlarge, there is central clearing wi
th desquamation.
9FF9.jpg|Fig. 9.9 ‘Localized’ pattern of pustular pso
riasis. The pustules are limited to preexisting plaques of psoriasis.
9FF10.jpg|Fig. 9.10 Pustulosis of the palms and soles. Multip
le sterile papules are admixed with yellow–brown macules on the palms.
9FF11.jpg|Fig. 9.11 Acrodermatitis continua of Hallopeau. Ery
thema and scale of the distal digit, pustules within the nail bed and partial sh
edding of the nail plate.
9FF12.jpg|Fig. 9.12 Inverse psoriasis. Shiny erythematous pla
ques in the axilla that lack scale. Courtesy of Ronald Rapini, M.D.
9FF13.jpg|Fig. 9.13 Nail psoriasis. Changes include distal on
ycholysis, pitting and oil spot phenomenon.
9FF14.jpg|Fig. 9.14 Sites of psoriatic arthritis and Reiter's dis
ease. Adapted from Braunwald E, Fauci AS, Kasper D, Hauser S, Longo D, James
on J. Harrison's Principles of Internal Medicine, 15th edn. New York: McGraw Hil
l. 2001; 1985.
9FF15.jpg|Fig. 9.15 Psoriatic arthritis. Asymmetric involveme
nt of the DIP and PIP joints. A ‘sausage’ digit (third digit bilater
ally) results from involvement of both the DIP and PIP joints.
9FF16.jpg|Fig. 9.16 Sneddon–Wilkinson disease. A Annula
r and polycyclic plaques in the axilla. B Subcorneal pustules with scale
and crusts.
9FF17.jpg|Fig. 9.17 Sneddon–Wilkinson disease. Note the
accumulation of the neutrophils in the dependent portion of the subcorneal pust
ule.
9FF18.jpg|Fig. 9.18 Subcorneal pustular dermatosis. The super
ficial site of the epidermal split is seen and the blister cavity is filled with
neutrophils.
9FF19.jpg|Fig. 9.19 Spongiform pustule of Kogoj. Collections
of neutrophils are seen within the stratum spinosum.
9FF20.jpg|Fig. 9.20 Microabscess of Munro. Remnants of neutro

phils are surrounded by parakeratosis.
9FF21.jpg|Fig. 9.21 Stable plaque psoriasis. Hyperplasia of t
he epidermis with ‘squared-off’ rete ridges, elongation of the derma
l papillae and parakeratosis.
9FF22.jpg|Fig. 9.22 Pustular psoriasis. Note the accumulation
of neutrophils in the stratum corneum and between the keratinocytes.
9FT1.jpg|Table 9.1 Cytokines relevant to potential therapies for
psoriasis. For a complete review on cytokines in psoriasis the reader is ref
erred to the literature58,59.
9FT2.jpg|Table 9.2 Cutaneous disorders associated with SAPHO.
Synovitis, acne, pustulosis, hyperostosis, osteitis; also referred to as chroni
c recurrent multifocal osteomyelitis.
9FT3.jpg|Table 9.3 Differential diagnosis of subcorneal/intraepid
ermal neutrophilic pustules. *Not all cases.
9FT4.jpg|Table 9.4 Vitamin D analogues. *To avoid hypercalcem
ia. **Maximum weekly amount for 8 weeks of treatment.
9FT5.jpg|Table 9.5 Indications and contraindications for vitamin
D3 analogues. *e.g. sarcoidosis, bone metastasis.
9FT6.jpg|Table 9.6 Indications and contraindications for topical
corticosteroids. Maximal quantities: 50 g/week of a superpotent corticostero
id; 100 g/week of a potent corticosteroid.
9FT7.jpg|Table 9.7 Indications and contraindications for dithrano
l. *Severe psoriasis usually treated in day-care center or inpatient setting
.
9FT8.jpg|Table 9.8 Indications and contraindications for topical
tazarotene in psoriasis.
9FT9.jpg|Table 9.9 Indications and contraindications for photo(ch
emo)therapy in psoriasis. *Need to adjust and monitor closely.
9FT10.jpg|Table 9.10 Indications and contraindications for methot
rexate. *Requires significant reduction in dosage. **Because of possible mut
agenic risk and teratogenicity, discontinue methotrexate 3 months prior to attem
pts to conceive; continue contraception during these 3 months.
9FT11.jpg|Table 9.11 Premethotrexate screening. Adapted from Said
et al.92. *Sometimes performed 2–4 months after the start
of methotrexate therapy.
9FT12.jpg|Table 9.12 Laboratory investigations during methotrexat
e treatment. Adapted from Said et al.92. *Perform 1 week after me
thotrexate administration because bone marrow suppression maximum at 7–10
days post-administration.
9FT13.jpg|Table 9.13 Side effects of methotrexate92,98
. *Same day or 2–3 days following methotrexate; may respond to folic a
cid, dose reduction or antiemetic drug. **May be reduced by folic acid. &#8
224;Up to 11% of patients on oral regimens. ‡Up to 25% of
patients receiving long-term therapy. ¶Two large series of psor
iasis patients, no increased risk of malignancy101,102.
9FT14.jpg|Table 9.14 Indications and contraindications for the us
e of cyclosporine for psoriasis. *Requires dose adjustment and careful monit
oring.
9FT15.jpg|Table 9.15 Precyclosporine screening.
9FT16.jpg|Table 9.16 Evaluation during cyclosporine treatment. For the first 3 months, once every 2–3 weeks; subsequently, once every 4
–6 weeks.
9FT17.jpg|Table 9.17 Indications and contraindications for acitre
tin in the treatment of psoriasis. *Requires dose adjustment and careful mon
itoring, e.g. phenytoin competes for plasma protein binding. **Reserved for trea
tment-resistant patients.
9FT18.jpg|Table 9.18 Preacitretin screening.
9FT19.jpg|Table 9.19 Evaluation during acitretin treatment.
10FF1.jpg|Fig. 10.1 The mycosis fungoides pyramid and the propose
d transitional role of clonal dermatitis in the evolution of mycosis fungoides.
10FF2.jpg|Fig. 10.2 Small plaque parapsoriasis. Small (<5
cm), erythematous, slightly scaly patches.
10FF3.jpg|Fig. 10.3 Large plaque parapsoriasis. Large, variab
ly erythematous and mildly poikilodermatous patches in the bathing trunk region.
10FF4.jpg|Fig. 10.4 Pityriasis lichenoides et varioliformis acuta
. Generalized, erythematous papules in various stages of evolution. Many of
the lesions are crusted.
10FF5.jpg|Fig. 10.5 Pityriasis lichenoides chronica. Multiple
red-brown papules, some with scale. No vesicles or pustules are seen. Courtesy
of Yale Residents Slide Collection.
10FF6.jpg|Fig. 10.6 Pityriasis lichenoides histopathology. Th
ere is a top-heavy, interface lymphoid infiltrate associated with extravasated e
rythrocytes, scale-crust, and focal epidermal destruction. This pathology reflec
ts an intermediate point in the PLC–PLEVA spectrum of disease.
10FF7.jpg|Fig. 10.7 Pityriasis rubra pilaris. Follicular papu
les and confluent orange-red scaly plaques with islands of sparing. Courtesy of
Yale Residents Slide Collection.
10FF8.jpg|Fig. 10.8 Pityriasis rubra pilaris. Diffuse erythro
derma with desquamation and follicular hyperkeratosis on knee. Courtesy of Yale
Residents Slide Collection.
10FF9.jpg|Fig. 10.9 Pityriasis rubra pilaris. Orange-red waxy
keratoderma of the palms. Courtesy of Larry Lantis MD.
10FF10.jpg|Fig. 10.10 Classification of pityriasis rubra pilaris
(PRP).
10FF11.jpg|Fig. 10.11 Pityriasis rubra pilaris. Psoriasiform
dermatitis with follicular plugging. Courtesy Ron Rapini, M.D.
10FF12.jpg|Fig. 10.12 Pityriasis rosea. Papules and annular p
laques.
10FF13.jpg|Fig. 10.13 Pityriasis rosea in darkly pigmented skin. It tends to be more papular than that in lightly pigmented skin. Note the as
sociated hyperpigmentation. Courtesy of Yale Residents Slide Collection.
10FF14.jpg|Fig. 10.14 Pityriasis rosea. Oval and round plaque
s, some with central scale and others with a collarette of scale. Courtesy of Ya
le Residents Slide Collection.
10FF15.jpg|Fig. 10.15 Inverse pityriasis rosea. Oval annular
plaques in groin. Courtesy of Yale Residents Slide Collection.
10FF16.jpg|Fig. 10.16 Pityriasis rosea. There is focal parake
ratosis, mild acanthosis, spongiosis, perivascular lymphocytes, and focal erythr
ocyte extravasation. Courtesy Ron Rapini M.D.
10FF17.jpg|Fig. 10.17 Granular parakeratosis. Papules with co
alescence into a plaque in the axilla. Courtesy of David Mehregan, M.D.
10FF18.jpg|Fig. 10.18 Axillary granular parakeratosis. Many f
ine granules are seen within the thickened stratum corneum. Courtesy Ron Rapini,
M.D.
10FT1.jpg|Table 10.1 Principal differential diagnosis of small pl
aque parapsoriasis (SPP) and large plaque parapsoriasis (LPP).
10FT2.jpg|Table 10.2 Therapeutic ladder for small plaque parapsor
iasis (SPP) and large plaque parapsoriasis (LPP). *Appropriate mainly for LP
P cases that meet the histopathologic criteria for patch-stage mycosis fungoides
. **If there is pruritus. Key to evidence-based support: (1) double-blind studie
s; (2) clinical series; (3) anecdotal.
10FT3.jpg|Table 10.3 Principal differential diagnosis of pityrias
is lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronic
a (PLC).
10FT4.jpg|Table 10.4 Therapeutic ladder for pityriasis lichenoide
s et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). *If
there is pruritus. **If there is secondary infection. ***If there is fever,
arthritis or other systemic findings. Key to evidence-based support: (1) double-
blind studies; (2) clinical series; (3) anecdotal.

11FF1.jpg|Fig. 11.1 Erythroderma with desquamation. Obvious e
xfoliation of scale with underlying erythema.
11FF2.jpg|Fig. 11.2 Crusted (Norwegian) scabies. Generalized
erythema with thick scale and crusted fissures on the plantar surface. Courtesy
of USC residents' slide collection.
11FF3.jpg|Fig. 11.3 Psoriatic erythroderma. Generalization af
ter withdrawal of methotrexate.
11FF4.jpg|Fig. 11.4 Psoriatic erythroderma. Nail changes (sub
ungual hyperkeratosis and distal dystrophy) indicating the underlying disease.
11FF5.jpg|Fig. 11.5 Sézary's syndrome. Diffuse erythema
with lichenification, hyperpigmentation and linear excoriations.
11FF6.jpg|Fig. 11.6 Pityriasis rubra pilaris. Note the island
of sparing.
11FF7.jpg|Fig. 11.7 Erythroderma due to pemphigus foliaceus.
Generalized erythema with superimposed scale crusts.
11FF8.jpg|Fig. 11.8 Approach to the differential diagnosis of adu
lt erythroderma.
11FT1.jpg|Table 11.1 Causes of erythroderma in adults. BMZ, b
asement membrane zone; DIF, direct immunofluorescence; IFF, indirect immunofluor
escence.
11FT2.jpg|Table 11.2 Causes of erythroderma in neonates and infan
ts. ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; SCID,
severe combined immunodeficiency.
11FT3.jpg|Table 11.3 Drugs associated with erythroderma.
11FT4.jpg|Table 11.4 The differential diagnosis of erythroderma i
n neonates and infants. el, eyelashes; eb, eyebrows; +, all of the cases; (+
), about half of the cases; -, rare/not found; ns, not specified). According to
Pruszkowski A, Bodemer C, Fraitag S, Teillac-Hamel D, Amorie JC, de Prost Y. Neo
natal and infantile erythrodermas: a retrospective study of 51 patients. Arch De
rmatol 2000;136:875–80.
12FF1.jpg|Fig. 12.1 Mouse model for the lichenoid tissue reaction
. Because in humans all the analyses are performed on existing skin lesions
(after the inflammatory response is underway), it is difficult to provide insigh
t into initiating events and to establish whether the T cells present are indeed
relevant to the pathogenesis. This experimentally induced animal model has the
advantage that the orchestrated series of events resulting in epidermal injury c
an be examined from the onset and over time.
12FF2.jpg|Fig. 12.2 Possible consequences of autoimmune attack by
T-cells. A There are several mechanisms by which epidermal keratinocytes un
dergo apoptosis in lichenoid tissue reactions. First, activated cytotoxic T lymp
hocytes (CTL) express Fas L, which binds to Fas expressed on epidermal keratinoc
ytes, resulting in apoptosis. Second, apoptosis can also be induced via the rele
ase of cytotoxic granules (perforin/granzyme). Although Fas/Fas L and perforin/g
ranzyme can independently trigger the cell death program, the process leading to
apoptosis is similar in both pathways. CD8+ CTL and NK cells use both pathways,
whereas Th1 cells preferentially use the Fas/Fas L pathway. These pathways are
useful for eliminating Fas-bearing abnormal keratinocytes (virally infected kera
tinocytes or transformed keratinocytes). The failure to eliminate these abnormal
keratinocytes results in the persistence of chronic inflammatory conditions. B Because keratinocytes are not only targets but also produce granzyme B, p
erforin and Fas L that can be used to protect the epidermis from immune-mediated
damage, keratinocytes should not be viewed merely as a victim of the immune-med
iated damage. Thus, Fas L-bearing keratinocytes can induce Fas-mediated death in
neighboring Fas-bearing T cells, resulting in the resolution of the lichenoid t
issue reaction. This pathway contributes to the elimination of potentially harmf
ul autoaggressive T cells. The relative balance of the ability to express Fas an
d Fas-L between T cells and keratinocytes would determine the outcome of the lic
henoid tissue reactions.
12FF3.jpg|Fig. 12.3 Various phases of LP. A In the induction
phase, dendritic cells present self-peptides modified by exogenous antigens (vir

uses, medications, and contact allergens) to antigen-specific naïve T cells
in the lymph nodes; the latter differentiate into effector T cells (Te). Self-p
eptides not modified by exogenous antigens are also shown. B In the evolution ph
ase, effector T cells (Te) that come to express skin-homing receptors (E-selecti
n ligands) migrate into the inflammatory site and, upon recognition of antigens,
are activated and release proinflammatory cytokines and cytotoxic granules, whi
ch in turn cause epidermal injury. C In the resolution phase, after the exogenou
s agents are cleared, these activated T cells either die or become memory T cell
s (Tm).
12FF4.jpg|Fig. 12.4 Lichen planus on the dorsal surface of the ha
nd. Wickham's striae can be easily identified in the upper right lesion. Not
e the flat-topped nature of the lesions.
12FF5.jpg|Fig. 12.5 Lichen planus. Violaceous papules and pla
ques with white scale and Wickham's striae.
12FF6.jpg|Fig. 12.6 Koebnerization of lichen planus into the site
of the excision of the saphenous vein. Lesions also appeared where steri-st
rips® had been supplied.
12FF7.jpg|Fig. 12.7 Annular lichen planus of the glans penis (A)
and the trunk (B).
12FF8.jpg|Fig. 12.8 Papulosquamous lesions of exanthematous LP on
the back.
12FF9.jpg|Fig. 12.9 Bullous lichen planus on the shin.
12FF10.jpg|Fig. 12.10 Hypertrophic lichen planus on the dorsal as
pect of the hands.
12FF11.jpg|Fig. 12.11 Lichen planopilaris. A Keratotic spines
surrounded by a violaceous rim in a linear variant and B scattered on th
e trunk. C Scarring alopecia with pseudopelade-like changes centrally, bu
t perifollicular inflammation at the margins.
12FF12.jpg|Fig. 12.12 Linear lichen planus. Discrete lesions
along the lines of Blaschko on the lower extremity of a child.
12FF13.jpg|Fig. 12.13 Nail lichen planus. A Thinning of the n
ail plate with lateral loss. B Violaceous discoloration of the periungual
area with pterygium formation.
12FF14.jpg|Fig. 12.14 Oral lichen planus. A White lacy patter
n on the buccal mucosa, the most common location for this form. B Multipl
e erosions on the tongue.
12FF15.jpg|Fig. 12.15 Histopathologic features of lichen planus. Hyperkeratosis, focal increase in the granular layer, saw toothing of the ep
idermis and a lichenoid infiltrate.
12FF16.jpg|Fig. 12.16 Lichen striatus. A Linear array of pink
flat-topped papules on the hand in association with dystrophy (splitting, frayi
ng) of L2 (lateral) and L3 (medial) nails. B Multiple streaks on the post
erior lower extremity of a child that resolved spontaneously. Courtesy of Yale R
esidents Slide Collection.
12FF17.jpg|Fig. 12.17 Lichen nitidus. A Numerous tiny flat-to
pped papules on the hand. B A close-up view shows the shiny surface. Cour
tesy of Yale Residents Slide Collection.
12FF18.jpg|Fig. 12.18 Histopathologic features of lichen nitidus. Note the typical ‘ball and claw’ configuration for the infiltra
te and epidermis, respectively. Several Langhans' giant cells are within the inf
iltrate.
12FF19.jpg|Fig. 12.19 Lichenoid drug eruptions. Photodistribu
ted lichenoid eruption due to HCTZ (note sparing under watchband).
12FF20.jpg|Fig. 12.20 Acute graft-versus-host disease, stage II. Pink macules and papules of the palms that are becoming confluent post-allog
eneic bone marrow transplant. Courtesy of Dennis Cooper, M.D.
12FF21.jpg|Fig. 12.21 Acute graft-versus-host disease, stage IV. Coalescence of bullae plus epidermal necrosis leading to large areas of denu
dation in a patient who had received allogenic BMT.
12FF22.jpg|Fig. 12.22 Chronic sclerodermoid graft-versus-host dis

ease. Morpheaform plaque with ulceration on the shoulder.
12FF23.jpg|Fig. 12.23 The histopathology of acute graft-versus-ho
st disease. Basal vacuolization with numerous apoptotic keratinocytes and a
lymphocytic infiltrate are seen; lymphocytes are present in both the epidermis a
nd papillary dermis. Courtesy of Dr Kayoko Matsunaga, Fujita Health University,
Nagoya, Japan.
12FF24.jpg|Fig. 12.24 Erythema dyschromicum perstans. Numerou
s, oval to polygonal, slate gray-colored macules diffusely distributed over the
buttock and back.
12FF25.jpg|Fig. 12.25 Keratosis lichenoides chronica. A Linea
r and stellate keratotic plaques. B Psoriasis-like scaling plaques on the
face. B, Courtesy of Dr Jiro Arata, Okayama University, Okayama, Japan.
12FT1.jpg|Table 12.1 Lichenoid dermatoses. *Acute and chronic
.
12FT2.jpg|Table 12.2 Therapeutic ladder for lichen planus. Sy
stemic treatments are usually reserved for more severe disease. Key to evidencebased support: 1, double-blind studies; 2, clinical series; 3, anecdote
12FT3.jpg|Table 12.3 Comparison of clinical and histological feat
ures of lichen nitidus versus lichen planus. *May be underestimated; **espec
ially darkly pigmented individuals.
12FT4.jpg|Table 12.4 Drugs implicated in lichenoid drug eruptions
.
12FT5.jpg|Table 12.5 Features for distinguishing lichenoid drug e
ruption from lichen planus *Especially with medications such as hydrochlorot
hiazide.
12FT6.jpg|Table 12.6 Clinical staging and histologic grading of a
cute graft-versus-host disease.
13FF1.jpg|Fig. 13.1 Cell-mediated immunopathogenesis in the acute
stage of atopic dermatitis. Langerhans cells (LC) in the epidermis enable c
apture of allergens and autoantigens, which are then internalized, processed and
packaged in MHC molecules on the LC surface and induce activation of T cells in
the draining lymph nodes and skin. Increased monocyte (Mo) PGE2 and IL-10 secre
tion directs T cell differentiation initially towards Th2 cells (CCR3+, CCR4+) w
ith IL-4, IL-5 and IL-13 over-expression. Th2 cells (with cutaneous lymphocyte a
ntigen molecule, CLA+) are recruited to the skin preferentially with the help of
chemokines produced by various cells in the skin, such as CCL17 (thymus and act
ivation regulated chemokine, TARC), CCL11 (eotaxin-1), and CCL5 (RANTES). B cell
s are associated with the production of IgE with the help of IL-4 and IL-13 secr
eted from Th2 cells. CD86 upregulation on B cells is associated with IgE synthes
is. Activated keratinocytes can also be stimulated by non-specific irritants, sc
ratching and superantigens, and produce TNFα, GM-CSF and chemokines critica
l for Th2 T cells (early) and Th1 cells (late). Moreover, activated mast cells (
MC) (e.g. cross-linking with FcεR1 on the cell surface) release TNFα,
IL-4 and IL-13, and together with CD40L on activated T cells enhance the express
ion of P-selectin, E-selectin, and VCAM-1 on endothelial cells. These molecules
further promote recruitment of cells from the blood.
13FF2.jpg|Fig. 13.2 Cell-mediated immunopathogenesis in the chron
ic stage of atopic dermatitis. In chronic lesions, Langerhans cells (LC) in
the epidermis after capturing and processing allergens/autoantigens and presenti
ng them to T cells find themselves in a different micro-milieu. GM-CSF is over-p
roduced in the thickened epidermis and can function to sustain antigen-presentin
g cells as well as infiltration of eosinophils and other leukocytes. Eosinophils
, elevated in the peripheral blood of AD patients, migrate into the dermis along
with monocytes (Mo) and T cells. Eosinophils are a source of IL-12, allowing a
transition to induction of Th1 differentiation with IFNγ production. In tur
n, IFNγ promotes monocytic/macrophagic/dendritic cell IL-12, further promot
ing Th1 differentiation. Activated keratinocytes and mast cells produce TNF&#945
;, upregulating the expression of P-selectin, E-selectin, and VCAM-1 on endothel
ial cells, thus recruiting more leukocytes from the blood. Moreover, TNFα,
particularly in combination with IFNγ, promotes production of chemokines su

ch as CCL9 (Mig), 10 (IP-10) and 11 (I-TAC), ligands for CXCR3, and CCL5, a liga
nd for CCR5 on Th1 cells, resulting in further recruitment of cells capable of T
h1 immune responses.
13FF3.jpg|Fig. 13.3 Postinflammatory depigmentation in atopic der
matitis. This patient had a widespread disease and multiple lesions of pruri
go nodularis. Courtesy of Jean Bolognia, M.D.
13FF4.jpg|Fig. 13.4 Atopic dermatitis on the face of an infant. Involvement of the cheeks is characteristic of the infantile pattern of AD.
13FF5.jpg|Fig. 13.5 Atopic dermatitis on the extensor surface of
an arm. This is characteristic of AD in this age group. Note the follicular
prominence on the trunk.
13FF6.jpg|Fig. 13.6 Adult with atopic dermatitis that favors the
face and neck.
13FF7.jpg|Fig. 13.7 Severe chronic hand dermatitis in an adult wi
th atopic dermatitis.
13FF8.jpg|Fig. 13.8 Atopic dermatosis with multiple linear excori
ations. This is a sign of scratching due to pruritus.
13FF9.jpg|Fig. 13.9 Keratosis pilaris. Monotonous perifollicu
lar papules with central keratotic cores on the extensor surface of the upper ar
m. There is also a peripheral rim of erythema.
13FF10.jpg|Fig. 13.10 African-American infant with atopic dermati
tis of the face. Note the Dennie–Morgan lines and central facial pallo
r.
13FF11.jpg|Fig. 13.11 Exaggerated palmar creases. This patien
t had AD and ichthyosis vulgaris. Courtesy of Jean Bolognia, M.D.
13FF12.jpg|Fig. 13.12 Pityriasis alba. Note the slight scale
associated with the hypopigmented macules and patches on the cheeks. Courtesy of
Anthony J Mancini, M.D.
13FF13.jpg|Fig. 13.13 Angular cheilitis. Scales and crusting
are prominent at the angles of the mouth. Courtesy of the Department of Dermatol
ogy, Hua Shan Hospital, Shanghai, China.
13FF14.jpg|Fig. 13.14 Lichen simplex chronicus in a young child w
ith atopic dermatitis. Exaggerated skin markings are seen on the extensor su
rfaces of the arm.
13FF15.jpg|Fig. 13.15 Lichen simplex chronicus in an adult with a
topic dermatitis. Note the preference for a flexure site.
13FF16.jpg|Fig. 13.16 Infected hand dermatitis in a patient with
AD. There is impetigo-like crusting as well as pustules. In sites with thinn
er stratum corneum, the latter are shorter lived.
13FF17.jpg|Fig. 13.17 Histologic features of acute and chronic at
opic dermatitis. A ‘Acute’ AD spongiosis in the epidermis with e
xocystosis of lymphocytes producing intraepidermal vesicles. B ‘Chr
onic’ AD. There is less spongiosis, with more irregular epidermal hyperpla
sia. Courtesy of Ron Rapini, M.D.
13FT1.jpg|Table 13.1 Diagnostic features of atopic dermatitis.
13FT2.jpg|Table 13.2 Diagnostic guidelines for atopic dermatitis8.
13FT3.jpg|Table 13.3 Causes of protein contact dermatitis.
13FT4.jpg|Table 13.4 Diagnostic features of atopic dermatitis as
suggested by the AAD consensus.
13FT5.jpg|Table 13.5 Differential diagnosis of atopic dermatitis.
 A, adults; B, both; C, children/infants.
13FT6.jpg|Table 13.6 Therapeutic ladder for atopic dermatitis. Ke
y to evidence based support: (1) double-blind studies; (2) clinical series; (3)
anecdotal.
14FF1.jpg|Fig. 14.1 Infantile seborrheic dermatitis. Glisteni
ng red plaques of the neck, axillary and inguinal folds. Note disseminated lesio
ns on the trunk and extremities. Courtesy of Robert Hartman, M.D.
14FF2.jpg|Fig. 14.2 Adult seborrheic dermatitis of the face and s

calp. A Sharply demarcated, symmetric erythema of forehead, nose, nasolabial
folds, and cheeks. B Note the scaling of the scalp.
14FF3.jpg|Fig. 14.3 Asteatotic eczema (eczema craquelé). A,
B The distal lower extremities have areas of erythema that contain a criss-c
ross pattern of superficial cracks and fissures said to resemble a dried river b
ed.
14FF4.jpg|Fig. 14.4 Stasis dermatitis. Dermatitis with oozing
and scale-crust surrounds a venous ulcer on the distal lower extremity.
14FF5.jpg|Fig. 14.5 Nummular dermatitis. Fairly well demarcat
ed discoid lesions of subacute and acute dermatitis. Courtesy of Kalman Watsky,
M.D.
14FF6.jpg|Fig. 14.6 Pityriasis alba. Hypopigmented macules an
d patches on the cheek of an African-American girl. Courtesy of Anthony Mancini,
M.D.
14FF7.jpg|Fig. 14.7 Juvenile plantar dermatosis in a child. E
rythema and scaling of the plantar surface of the great toes and ball of the foo
t bilaterally. Note the glazed appearance of the skin of the left foot. Courtesy
of Kalman Watsky, M.D.
14FT1.jpg|Table 14.1 Differential diagnosis of dermatitis of the
foot.
15FF1.jpg|Fig. 15.1 Allergic contact dermatitis. Linear strea
ks seen with ACD to poison ivy. Note the edema and vesicle formation.
15FF2.jpg|Fig. 15.2 Allergic contact dermatitis. Chronic hand
dermatitis due to ACD to mercaptobenzothiazole found in rubber gloves.
15FF3.jpg|Fig. 15.3 Chronic allergic contact dermatitis leading t
o hand dermatitis. This golfer wore one leather glove and had positive patch
tests to potassium dichromate and a piece of his glove. Courtesy of Kalman Wats
ky, M.D.
15FF4.jpg|Fig. 15.4 Allergic contact dermatitis to leather shoes.
 Note the correspondence to sites of exposure. Courtesy of Yale Residents Sl
ide Collection.
15FF5.jpg|Fig. 15.5 Acute allergic dermatitis to poison ivy.
In addition to crusted and weeping plaques, there is periorbital edema. Courtesy
of Jean Bolognia, M.D.
15FF6.jpg|Fig. 15.6 Acute bullous allergic contact dermatitis due
to poison ivy. This distribution is seen in patients who wear gloves. Court
esy of Yale Residents Slide Collection.
15FF7.jpg|Fig. 15.7 Acute contact dermatitis due to aloe-containi
ng cream. The degree of involvement on the upper and lower lips is similar.
15FF8.jpg|Fig. 15.8 Chronic allergic contact dermatitis due to gl
utaraldehyde. The patient was an optometrist.
15FF9.jpg|Fig. 15.9 Allergic contact dermatitis due to cashew nut
shell oil. This represented an occupational exposure. Courtesy of Yale Resi
dents Slide Collection.
15FF10.jpg|Fig. 15.10 Irregular psoriasiform epidermal hyperplasi
a with slight spongiosis. A The thick compact orthokeratotic stratum corneum
is due to the acral location of the specimen. B Spongiotic, vesicular ps
oriasiform dermatitis due to contact dermatitis. The intraepidermal vesiculation
is a consequence of marked spongiosis. C Spongiotic, psoriasiform dermat
itis with areas of spongiotic microvesiculation within the epidermis. D H
igher magnification of C showing eosinophils within a spongiotic microves
icle at the tip of a rete ridge. Eosinophils were also present in the dermal inf
iltrate.
15FF11.jpg|Fig. 15.11 Allergens contained within syringes being p
laced by nurse into Finn chambers.
15FF12.jpg|Fig. 15.12 Fixing allergens to patient's back using Sc
anpor® tape.
15FF13.jpg|Fig. 15.13 Skin impressions of Finn chamber owing to g
ood adherence.
15FF14.jpg|Fig. 15.14 Allergens being marked upon removal of Scan

por® tape.
15FF15.jpg|Fig. 15.15 A positive patch test reaction +++.
15FF16.jpg|Fig. 15.16 A positive patch test reaction to nickel. This is an example of a +++ reaction.
15FF17.jpg|Fig. 15.17 Hand dermatitis in a florist with positive
patch test to alstroemeria. Alstroemeria are the reddish flowers on the left
-hand side of the bouquet.
15FF18.jpg|Fig. 15.18 ACD to fragrance found in cologne. A Pa
tient with ACD to fragrance found in his cologne. B Patient after avoidan
ce of fragrances and his cologne.
15FF19.jpg|Fig. 15.19 Approach to the patient with suspected cort
icosteroid allergy.
15FF20.jpg|Fig. 15.20 Systemic contact dermatitis. This patie
nt who was previously sensitized to ethylenediamine received aminophylline.
15FT1.jpg|Table 15.1 Components of the North American Contact Der
matitis Group (NACDG) Screening Series, the European Standard Series and the TRU
E® Test Series.
15FT2.jpg|Table 15.2 International Grading System for patch tests
.
15FT3.jpg|Table 15.3 Exposure information sheet: Balsam of Peru (
Myroxylon pereirae). With permission from Marks et al 12 p 110, Balsam of Peru exposure sheet
15FT4.jpg|Table 15.4 Top ten allergens as identified by the North
American Contact Dermatitis Group. Adapted from North American Contact Derm
atitis Group Patch Test Results, 1996–1998. Arch Dermatol. 2000;136:272&#8
211;3. Copyrighted 2000, American Medical Association.
15FT5.jpg|Table 15.5 Other top allergens identified by the North
American Contact Dermatitis Group. FR, formaldehyde releaser.
15FT6.jpg|Table 15.6 Corticosteroid classes and patch test concen
trations. *Available without prescription in the US. †Sugge
sted screening agents. In petrolatum unless stated otherwise. Eth, Ethanol; Pet,
petrolatum; parentheses contain other, suggested concentrations or vehicles.
15FT7.jpg|Table 15.7 Examples of topical allergens that may resul
t in systemic contact dermatitis with systemic exposure.
16FF1.jpg|Fig. 16.1 Bilateral shoe irritant dermatitis resulting
from chronic occlusive footwear.
16FF2.jpg|Fig. 16.2 Irritant dermatitis of the face due to irrita
nt chemicals. This may be induced secondary to topical acne polytherapy incl
uding salicylic acid, glycolic acid, retinoids, bleaching agents and vitamin E.
16FF3.jpg|Fig. 16.3 Professional paint and crayon illustrator wit
h bilateral palmar dermatitis secondary to repeated contact with paint solvents. Extensive patch testing excluded allergic contact dermatitis.
16FF4.jpg|Fig. 16.4 Practicing dentist with moderately severe irr
itant hand dermatitis from chronic exposure to disinfecting solutions and antise
ptics. The results of patch testing, latex challenge testing, and RAST testi
ng were negative.
16FF5.jpg|Fig. 16.5 A classification of hand dermatitis.
16FT1.jpg|Table 16.1 Causes of occupational irritant contact derm
atoses in Finland during 1990–2000 (Total of 4823 cases). Tammilehto L
., Finnish Register of Occupational Diseases, 2001.
16FT2.jpg|Table 16.2 Irritants and mechanisms of toxicity.
16FT3.jpg|Table 16.3 Clinical features suggesting an irritant or
toxic etiology.
17FF1.jpg|Fig. 17.1 Relative frequency of occupational skin disea
ses in UK1. 
17FF2.jpg|Fig. 17.2 Materials attributed as causes of contact der
matitis by occupational physicians in the UK.
17FF3.jpg|Fig. 17.3 Prevalence of dermatitis by occupation in the
UK (annual rate per 100 000 employed)2.
17FF4.jpg|Fig. 17.4 Initial subclinical response to tissue pertur

bation by an irritant becomes manifest as chronic irritant dermatitis after repe
ated insults. Each arrow represents an irritant insult of different intensit
y.
17FF5.jpg|Fig. 17.5 Hand of a builder who presented with a pompho
lyx pattern of eczema. Investigation demonstrated contact allergic dermatiti
s to chromate found in cement and contact urticaria to latex in the gloves he wa
s using for hand protection.
17FF6.jpg|Fig. 17.6 The effects of mechanical injury to the skin.
 Adapted from Adams RM. Occupational skin disease. 3rd edition. Phila
delphia: W.B. Saunders 1999:36.
17FF7.jpg|Fig. 17.7 Treatment of tinea with topical corticosteroi
d resulted in an appearance resembling dermatitis.
17FF8.jpg|Fig. 17.8 Relative frequency of occupational contact ur
ticaria to various urticants in Finland.
17FF9.jpg|Fig. 17.9 Relative risk of developing contact urticaria
by occupation.
17FF10.jpg|Fig. 17.10 Contact urticaria of the fingers after wear
ing latex rubber gloves. Although signs can be subtle, the implications of m
aking the diagnosis are significant.
17FF11.jpg|Fig. 17.11 Approach to the patient with suspected late
x allergy.
17FF12.jpg|Fig. 17.12 Positive prick test with a commercial latex
extract and high ammoniated natural rubber latex. Histamine and saline cont
rols are appropriately positive and negative.
17FF13.jpg|Fig. 17.13 Chloracne. Note heavy involvement of re
troauricular skin with comedones and cysts.
17FF14.jpg|Fig. 17.14 Chloracne. Closed and open comedones wi
th red papules are seen.
17FT1.jpg|Table 17.1 Clinical classification of occupational derm
atoses.
17FT2.jpg|Table 17.2 Points to consider when taking an occupation
al history.
17FT3.jpg|Table 17.3 Suggested concentrations for patch testing s
elected work materials*.
18FF1.jpg|Fig. 18.1 Causes and types of chronic hand or finger ec
zema due to plants.
18FF2.jpg|Fig. 18.2 Stinging nettle (Urtica dioica). (
A) Habit seen on Kansas prairie. Photo courtesy of Craig A. Freeman, with
permission from Cutis® (2001;67:193); ©2001 Quadran
t Health Com Inc. (B) Trichomes on leaf edge of stinging nettle (Urtic
a dioica). (C) Trichomes on stem of stinging nettle (Urtica dioica
). (D) Broken trichome from stinging nettle (Urtica dioica). A
bubble is visible where urticating chemicals are found.
18FF3.jpg|Fig. 18.3 Prickly pears (Opuntia spp.) and their
glochids. (A) Microscopic appearance of glochids from Opuntia mic
rodasys. (B) Prickly pear (Opuntia ficus-indica) habit. (C) Prickly pear (Opuntia ficus-indica) fruit. Fine spines and glochids
are visible. Courtesy of Dirk Elston, M.D.
18FF4.jpg|Fig. 18.4 Erythematous, burning, edematous scrotum from
irritant reaction after applying garlic (Allium sativum) to treat rash. Courtesy of Dr Martin Giandoni.
18FF5.jpg|Fig. 18.5 Apiaceae. Compound umbels can be umbrella
-shaped or ball-shaped.
18FF6.jpg|Fig. 18.6 Early vesicular reaction of phytophotodermati
tis. Courtesy Fitzsimons Army Medical Center Dermatology slide teaching libr
ary.
18FF7.jpg|Fig. 18.7 Phytophotodermatitis. Streaky hyperpigmen
tation due to phytophotodermatitis from accidental contact due to a weed of the
family Apiaceae (Umbelliferae). This mild reaction was not preceded by erythema
or vesicles.
18FF8.jpg|Fig. 18.8 Characteristic features useful for identifyin
g poison ivy, poison oak and poison sumac. With permission from the Ameri
can Journal of Contact Dermatitis.
18FF9.jpg|Fig. 18.9 Geographic range of Toxicodendron spec
ies.
18FF10.jpg|Fig. 18.10 Leaves and seeds of Ginkgo biloba. Only the fresh seed covering contains the allergen, ginkgolic acid, which typ
ically cross-reacts with urushiol.
18FF11.jpg|Fig. 18.11 Typical composite flower heads of member of
the family Asteraceae (Compositae). Note the leaf-like bracts underneath th
e flower head. Daisy (Leucanthemum spp.), demonstrating composite flower
head (A) and leaf-like bracts beneath the flower head (B) that are
characteristic of flower heads of the family Asteraceae. C A cush
ion chrysanthemum (X Dendranthema cvs), demonstrating all ray, or strap-l
ike florets. D A composite chrysanthemum (X Dendranthema cvs) demo
nstrating central tubular florets and peripheral ray florets. This composite typ
e of flower head gave rise to the former family name Compositae.
18FF12.jpg|Fig. 18.12 Clinical manifestations of Anacardiaceae de
rmatitis. A Acute, streak-like edematous and erythematous dermatitis without
vesicles after poison ivy brushed across the face. Courtesy of Fitzsimons Army
Medical Center Dermatology slide teaching library. B Acute, streak-like v
esicular dermatitis after poison ivy (Toxicodendron radicans) contact. Co
urtesy of Fitzsimons Army Medical Center Dermatology slide teaching library. 
C Widespread erythema and edema associated with intense pruritus after carry
ing logs of the poisonwood tree (Metopium toxiferum) of the family Anacar
diaceae. D ‘Black-spot’ poison ivy dermatitis: note the black
discoloration in the central portion of the edematous plaques due to plant resi
n.
18FF13.jpg|Fig. 18.13 Some house plants known to commonly cause d
ermatoses.
18FF14.jpg|Fig. 18.14 Airborne contact dermatitis. Example of
the airborne contact dermatitis pattern seen in a patient allergic to sesquiter
pene lactones. Note involvement on the anterior neck, which would not be expecte
d if this were a photodermatitis. Courtesy of Dirk Elston, M.D.
18FF15.jpg|Fig. 18.15 Allergic contact dermatitis. (A)
Flowers of the Peruvian lily (Alstroemeria spp.). (B) Florist wit
h fingertip Alstroemeria allergic contact dermatitis showing how he holds
Peruvian lily while cutting off the leaves. (B and D with permiss
ion from the American Journal of Contact Dermatitis.) (C) Thumb an
d (D) index finger of same florist, showing the chronic, lichenified, hyp
erkeratotic dermatitis caused by allergy to Peruvian lily and tulipalin A (Al
stroemeria).
18FF16.jpg|Fig. 18.16 An umbrella-shaped compound umbel is seen o
n wild carrot (Daucus carota).
18FF17.jpg|Fig. 18.17 A ball-shaped compound umbel seen in dill (Anethum graveolens).
18FF18.jpg|Fig. 18.18 Mature gingko tree (Gingo biloba). These have become popular in urban centers in temperate climates because of t
heir beauty and high resistance to air pollution and insects.
18FF19.jpg|Fig. 18.19 Bilobed leaf of Gingko biloba (hence
the name biloba).
18FT1.jpg|Table 18.1 The basic nomenclatural scheme for plants, u
sing common poison ivy as the example. The distinctive ending for each categ
ory is underlined. Note that the minor categories of nomenclature have no specia
l endings.
18FT2.jpg|Table 18.2 Some of the many plants implicated as causes
of immunologically mediated urticaria. Those in bold have also been demonst
rated to cause protein contact dermatitis. Any plant can probably cause urticari
a, and this list probably reflects frequency of contact.
18FT3.jpg|Table 18.3 The most common plants causing toxin-mediate

d urticaria6
18FT4.jpg|Table 18.4 Common plants known to cause mechanical irri
tant reactions. Although numerous plants possess irritant appendages, some o
f the well-known ones are listed below.
18FT5.jpg|Table 18.5 Plants most commonly implicated in causing c
hemical irritant dermatitis.
18FT6.jpg|Table 18.6 Important members of the Apiaceae family (fo
rmerly Umbelliferae) implicated in phototoxic reactions.
18FT7.jpg|Table 18.7 Phototoxic members of the family Rutaceae.
18FT8.jpg|Table 18.8 Risk activities for phytophotodermatitis.
18FT9.jpg|Table 18.9 Most common allergenic members of the Anacar
diaceae family and members of two other plant families that also contain urushio
l crossreacting chemicals.
18FT10.jpg|Table 18.10 Some of the more than 200 allergenic membe
rs of Compositae found throughout temperate world climates25. SQL
, sesquiterpene lactone.
18FT11.jpg|Table 18.11 Most common plant dermatoses. These ar
e admittedly biased by the anecdotal and unscientific observations of the author
. ACD, allergic contact dermatitis; ICD, irritant contact dermatitis.
19FF1.jpg|Fig. 19.1 Wheals. The wheals are often pruritic, pi
nk superficial dermal swellings that have pale centers.
19FF2.jpg|Fig. 19.2 Angioedema swellings are deeper than wheals a
nd may affect mucosal sites. They are often pale and poorly defined.
19FF3.jpg|Fig. 19.3 Mast cell degranulating stimuli.
19FF4.jpg|Fig. 19.4 Medicators released by dermal mast cell degra
nulation. Preformed and newly synthesized proinflammatory mediators in mast
cells.
19FF5.jpg|Fig. 19.5 Histamine-releasing autoantibodies bind the e
xtracellular α subunit of the high-affinity IgE receptor (FcεRI).
Autoantibodies directed against the terminal α1 domain are able
to bind the receptor in the presence of IgE and are therefore non-competitive, w
hereas those recognizing the α2 domain compete with IgE for the
binding site.
19FF6.jpg|Fig. 19.6 Regulatory role of C1 esterase inhibitor on t
he fibrinolytic, coagulation, complement and kinin systems.
19FF7.jpg|Fig. 19.7 Causes of acute urticaria.
19FF8.jpg|Fig. 19.8 Causes of chronic urticaria.
19FF9.jpg|Fig. 19.9 Symptomatic dermographism within minutes of s
cratching.
19FF10.jpg|Fig. 19.10 Delayed pressure urticaria on the shoulder
2 hours after carrying a heavy pipe.
19FF11.jpg|Fig. 19.11 Cholinergic urticaria on the trunk after ex
cercising and sweating.
19FF12.jpg|Fig. 19.12 Cold urticaria on an elbow after immersion
in iced water for 10 minutes, followed by rewarming.
19FF13.jpg|Fig. 19.13 Lesions of urticarial vasculitis that look
like ordinary urticaria but which last longer and may bruise.
19FF14.jpg|Fig. 19.14 Allergic contact urticaria (arrows) to late
x from a rubber glove.
19FF15.jpg|Fig. 19.15 Non-immunological contact urticaria from a
nettle sting.
19FF16.jpg|Fig. 19.16 Histology of a spontaneous wheal showing de
rmal edema, a dilated vessel, and a mild perivascular infiltrate of lymphocytes,
neutrophils and eosinophils.
19FF17.jpg|Fig. 19.17 Approach to the diagnosis of chronic urtica
ria.
19FF18.jpg|Fig. 19.18 A pink wheal response is present at the sit
e of an intradermal injection of autologous serum, but not at that of a normal s

aline control. Spontaneous wheals are also present at the venipuncture site
and away from the skin tests.
19FF19.jpg|Fig. 19.19 Management of ordinary and physical chronic
urticaria.
19FT1.jpg|Table 19.1 Etiologies and pathomechanisms of urticarial
lesions. It is often difficult to know the exact pathogenesis of individual
cases of urticaria, and many cases remain idiopathic after evaluation.
19FT2.jpg|Table 19.2 Clinical classification of urticaria and ang
ioedema. All clinical patterns of urticaria can be acute, episodic or chroni
c
19FT3.jpg|Table 19.3 Classification of physical urticarias by the
eliciting stimulus
19FT4.jpg|Table 19.4 Antihistamines for chronic urticaria. A
short-acting classic antihistamine may be added at night to a daily second- or t
hird-generation antihistamine, with or without the addition of an H2
antagonist for maximal antihistamine blockade. *Current prescribing manuals shou
ld be consulted for details on doses in children. ( ) = evidence category: 1, do
uble-blind study; 2, clinical trial.
19FT5.jpg|Table 19.5 Some second-line medications for chronic urt
icaria. *Current prescribing manuals should be consulted for details on dose
, drug interactions and contraindications for individual patients. The stated do
ses represent guidelines only. ( ) = evidence category: 1, double-blind study; 2
, clinical trial; 3, anecdotal case reports.
20FF1.jpg|Fig. 20.1 Superficial form of erythema annulare centrif
ugum. An annular plaque with delicate scaling on the inner margin of the adv
ancing edge (trailing scale).
20FF2.jpg|Fig. 20.2 Erythema annulare centrifugum. The lesion
s have no scaling and are similar in appearance to annular urticaria but are not
evanescent.
20FF3.jpg|Fig. 20.3 Erythema marginatum (rheumaticum). Polycy
clic and evanescent annular lesions are seen on the trunk of this young patient.
20FF4.jpg|Fig. 20.4 Erythema marginatum (rheumaticum). Faint
evanescent annular and arciform erythema in a patient with streptococcal pharyng
itis and arthralgias. Courtesy Ronald Rapini, M.D.
20FF5.jpg|Fig. 20.5 Erythema (chronicum) migrans. Annular ery
thema that spreads centrifugally. The peripheral erythematous border may or may
not be sharply demarcated and is usually 1–2 cm in width.
20FF6.jpg|Fig. 20.6 Erythema gyratum repens. Multiple gyrate
erythematous plaques, showing a wood-grain pattern. Courtesy of Agustín Alo
mar, M.D.
20FF7.jpg|Fig. 20.7 Erythromelalgia. A red, hot and painful h
and. In addition, there is a superficial erosion on the thenar eminence. Courtes
y of Agustín Alomar, M.D.
20FT1.jpg|Table 20.1 Differential diagnosis of figurate erythemas
. Both histologic findings and key clinical features are provided.
21FF1.jpg|Fig. 21.1 Phenotypic variety in EM. A Edematous/urt
icarial; B urticarial lesions with central crusting; C rythematous
plaques with dusky centers; D classic target lesions on the palms. Court
esy of Yale Residents Slide Collection.
21FF2.jpg|Fig. 21.2 Isomorphic phenomenon in EM. Target lesio
ns developing linearly along a preceding animal scratch.
21FF3.jpg|Fig. 21.3 Mucosal erosions and serous crusting with an
outer zone of color change on the lips in HSV-associated EM. Note the two zo
nes of color change on adjacent skin.
21FF4.jpg|Fig. 21.4 Histology of a target lesion in erythema mult
iforme. An interface dermatitis is present with exocytosis, apoptotic kerati
nocytes, and a perivascular mononuclear cell infiltrate.
21FF5.jpg|Fig. 21.5 Hemorrhagic crusts and denudation of the lips
associated with bullous cutaneous lesions associated with childhood SJS seconda
ry to trimethoprim–sulfamethoxazole therapy.
21FF6.jpg|Fig. 21.6 Denuded lesions of the lips with minimal cuta
neous lesions in a child with SJS secondary to antibiotic therapy. Courtesy
of Yale Residents Slide Collection.
21FF7.jpg|Fig. 21.7 Severe conjunctival erosions and exudate in S
JS secondary to trimethoprim–sulfamethoxazole therapy.
21FF8.jpg|Fig. 21.8 Clinical features of Stevens–Johnson sy
ndrome.
21FF9.jpg|Fig. 21.9 Dusky purple-red macules on the palms in a ch
ild with SJS.
21FF10.jpg|Fig. 21.10 Erosions of the genital mucosa in a woman w
ith SJS. Courtesy of Yale Residents Slide Collection.
21FF11.jpg|Fig. 21.11 Approach to the patient with Stevens–
Johnson syndrome.
21FT1.jpg|Table 21.1 Differences between erythema multiforme and
urticaria.
21FT2.jpg|Table 21.2 Precipitating factors in Stevens–Johns
on syndrome.
21FT3.jpg|Table 21.3 Relative risk of life-threatening drug react
ions (Stevens–Johnson syndrome/toxic epidermal necrolysis) among patients
using anticonvulsants31.
21FT4.jpg|Table 21.4 Differential diagnosis of Stevens–John
son syndrome and toxic epidermal necrolysis.
21FT5.jpg|Table 21.5 Differential diagnosis of Stevens–John
son syndrome, Kawasaki disease and paraneoplastic pemphigus.
22FF1.jpg|Fig. 22.1 Histology of toxic epidermal necrolysis (TEN)
. A Histology of an early-stage lesion of TEN. Arrows: apoptotic keratinocyt
es. B Histology of a late-stage lesion of TEN featuring separation of the
epidermis from the dermis, and full-thickness necrosis of the epidermis.
22FF2.jpg|Fig. 22.2 The Fas signaling pathway of apoptotic cell d
eath. The death receptor Fas and its ligand FasL are transmembrane proteins.
Fas signaling is triggered in the target cells by receptor tri(multi)-merizatio
n, induced upon contact with membrane-bound FasL from an adjacent cell. Subseque
ntly, recruitment of intracellular signaling proteins FADD and pro-caspase-8 lea
ds to autoactivation of the protease caspase-8 and apoptosis due to subsequent a
ctivation of downstream effector caspases (caspases-3, -6, -7), which cause cell
ular disintegration and death.
22FF3.jpg|Fig. 22.3 The keratinocyte Fas–FasL system in nor
mal skin and its role in toxic epidermal necrolysis (TEN) and treatment with IVI
G. A In normal skin, low levels of FasL are expressed by keratinocytes and l
ocalized intracellularly. B In lesional skin of TEN, high levels of FasL
are expressed by keratinocytes and localized on the cell surface. Upon contact w
ith Fas, cell surface FasL induces Fas multimerization and rapid signaling leadi
ng to keratinocyte cell death by apoptosis. C Inhibition by intravenous i
mmunoglobulins (IVIG) due to their content of naturally occurring antibodies tha
t bind to and block the function of the Fas receptor.
22FF4.jpg|Fig. 22.4 Cutaneous features of toxic epidermal necroly
sis (TEN). A Characteristic dusky-red color of the early macular eruption in
TEN. Lesions with this color often progress to full-blown necrolytic lesions wi
th dermo-epidermal detachment. B Positive Nikolsky sign: epidermal detach
ment reproduced by mechanical pressure on an area of erythematous skin.
22FF5.jpg|Fig. 22.5 Clinical features of toxic epidermal necrolys
is (TEN). A Detachment of large sheets of necrolytic epidermis (>30% bod
y surface area), leading to extensive areas of denuded skin. B Hemorrhagi
c crusts with mucosal involvement. C Epidermal detachment of palmar skin.
22FF6.jpg|Fig. 22.6 Stevens–Johnson syndrome (SJS) versus S
JS–TEN overlap. In addition to mucosal involvement and widespread eryt
hematous papules, there are small areas of epidermal detachment (arrows). Becaus
e the latter involve <10% body surface area, the patient is classified as ha
ving SJS.
22FF7.jpg|Fig. 22.7 In vitro inhibition of Fas-mediated ke

ratinocyte apoptosis by high-dose intravenous immunoglobulin (IVIG). Viabili
ty of normal human keratinocytes and the HaCaT keratinocyte cell line when expos
ed to recombinant cytolytically active human FasL. Preincubation conditions cons
isted of vehicle alone (control cells), IVIG (30 mg/ml), or albumin (30&nbs
p;mg/ml).
22FF8.jpg|Fig. 22.8 Treatment of toxic epidermal necrolysis (TEN)
. Facial involvement of a patient with TEN (50% body surface area involvemen
t) before (A) and 3 weeks after (B) treatment with intravenous imm
unoglobulin (0.75 g/kg/day for 4 days).
22FT1.jpg|Table 22.1 Clinical features that distinguish Stevens&#
8211;Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS–TEN
overlap. BSA, body surface area.
22FT2.jpg|Table 22.2 Medications most frequently associated with
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). F
or a complete updated list of drugs associated with SJS and TEN, refer to: Litt
JZ. Drug Eruption Reference Manual. New York: Parthenon Publishing Group. . 1Antibacterial; 2Sedative/hypnotic; 3NSAID; *Not av
ailable in the US.
22FT3.jpg|Table 22.3 SCORTEN severity-of-illness score.
23FF1.jpg|Fig. 23.1 Exanthematous drug eruptions. Numerous pi
nk papules on the trunk due to a cephalosporin (A). Confluence of lesions
on the trunk (B) and annular plaques on the forehead (C) secondar
y to phenobarbital.
23FF2.jpg|Fig. 23.2 Urticaria secondary to penicillin. Severa
l of the lesions have a figurate appearance.
23FF3.jpg|Fig. 23.3 Phototoxic reaction in a patient receiving me
thotrexate. The erythema and bullae are obviously limited to sun-exposed sit
es and resemble an exaggerated sunburn. Patients on methotrexate can also experi
ence a ‘sunburn-recall’ phenomenon.
23FF4.jpg|Fig. 23.4 Photolichenoid drug eruption due to hydrochlo
rothiazide. The lesions favored the extensor surfaces of the forearms.
23FF5.jpg|Fig. 23.5 Classification of sulfonamides. *Often co
mbined with other anti-hypertensives, e.g. triamterene, ACE inhibtors, β-bl
ockers. **Eyedrops. Adapted from Searle/Pfizer handout.
23FF6.jpg|Fig. 23.6 Acute generalized exanthematous pustulosis (A
GEP). Diffuse erythema of the buttock (A) and face (B) studded
with sterile pustules. Spongiform pustules are seen withing the epidermis of le
sional skin (C). A Due to cephalosporin and B due to metron
idazole. B Courtesy of Kalman Watsky, M.D.
23FF7.jpg|Fig. 23.7 Local reaction due to vitamin K injection.
23FF8.jpg|Fig. 23.8 Iododerma. Edematous erythematous papules
on the buttocks with central crusts.
23FF9.jpg|Fig. 23.9 Neutrophilic eccrine hidradenitis. Erythe
matous plaques on the leg which may be confused with Sweet's syndrome.
23FF10.jpg|Fig. 23.10 Drug rash with eosinophilia and systemic sy
mptoms (DRESS). Note the edema of the face as well as edematous pink papules
in this woman who had taken carbamazepine.
23FF11.jpg|Fig. 23.11 Fixed drug eruptions. Well-demarcated e
rythematous (A) to violet-brown plaques that can develop a detached epide
rmis (B) or erosion (C) centrally. As lesions heal, circular areas
of hyperpigmentation are commonly seen (D). Responsible drugs were pheno
phthalein (A), naproxen (B), ciprofloxin (C), and trimethop
rim-sulfamethoxazole (D). C Courtesy of Kalman Watsky, M.D. D Courtesy of Jean Bolognia, M.D.
23FF12.jpg|Fig. 23.12 Stevens-Johnson syndrome. Epidermal det
achment (A) and involvement of the conjunctivae (B).
23FF13.jpg|Fig. 23.13 Heparin-induced necrosis. Note the isch
emia of the skin. Courtesy of Kalman Watsky, M.D.
23FF14.jpg|Fig. 23.14 Heparin-associated thrombocytopenia. Bo

th petechiae and areas of cutaneous necrosis due to thrombosis are seen. Courtes
y of Jean Bolognia, M.D.
23FF15.jpg|Fig. 23.15 Serum sickness due to anti-thymocyte globul
in. The purpuric lesions are due to small-vessel vasculitis in this patient
with aplastic anemia. Courtesy of Jean Bolognia, M.D.
23FF16.jpg|Fig. 23.16 Sites of action of chemotherapeutic agents.
 PALA, N-phosphonoacetyl-L-aspartate; TMP, thymidine monophosphate.
23FF17.jpg|Fig. 23.17 Cutaneous side-effects of chemotherapeutic
agents. A Ulceration due to extravasation of doxorubicin. B Horizonta
l melanonychia due to 5-fluorouracil. C Erythema of the ears due to the c
ytarabine (cytosine arabinoside), sometimes referred to as ‘Ara-C ears&#82
17;; the petechiae are due to thrombocytopenia. D Erythrodysesthesia due
to cytarabine with obvious erythema of the plantar surface. E Necrosis of
psoriatic plaques due to an ‘overdose’ of methotrexate. F Ra
ynaud's phenomenon and digital necrosis due to systemic bleomycin. B–E Courtesy of Jean Bolognia, M.D.
23FF18.jpg|Fig. 23.18 Gray discoloration of the face due to amiod
arone. Biopsy specimens demonstrate yellow-brown granules within dermal macr
ophages.
23FT1.jpg|Table 23.1 Skin reactions to ‘drugs’ receiv
ed by at least 1000 patients1.
23FT2.jpg|Table 23.2 Drugs received by more than 1000 patients wi
th no skin reactions (rates estimated to be ≤3 per 1000)1.
23FT3.jpg|Table 23.3 Mechanisms of cutaneous drug-induced reactio
ns.
23FT4.jpg|Table 23.4 Logical approach to determine the cause of a
drug eruption. *Often inadvertant.
23FT5.jpg|Table 23.5 Characteristics of major drug-induced erupti
ons. *Also referred to as hypersensitivity syndrome. **Nonpigmenting.
23FT6.jpg|Table 23.6 Reactions localized to sites of injections o
f medications (in addition to extravasation of those administered intravenously)
.
23FT7.jpg|Table 23.7 SCORTEN. It represents a prognostic scor
ing system for patients with TEN. The score is based upon the number of prognost
ic factors in a particular patient. BSA, body surface area.
24FF1.jpg|Fig. 24.1 Clinical examples of petechia. A Round to
oval petechia, <3 mm in diameter); B actinic (solar) purpura (m
acular ecchymoses in sites of actinic damage plus trauma); C palpable pur
pura due to small vessel vasculitis (inflammation plus hemorrhage); and D
non-inflammatory (bland) retiform purpura lesions in a patient with disseminate
d intravascular coagulation (DIC).
24FF2.jpg|Fig. 24.2 Differential diagnosis of purpura.
24FF3.jpg|Fig. 24.3 Time course for immune complex-mediated leuko
cytoclastic vasculitis lesions. A Time course for immune complex-mediated le
ukocytoclastic vaculitis lesions. B Time course of microvascular occlusio
n-related lesions.
24FF4.jpg|Fig. 24.4 Coagulation-related pathways.
24FF5.jpg|Fig. 24.5 Chronic pigmented purpura, Schamberg variant
in a child. Yellow patches with superimposed petechiae.
24FT1.jpg|Table 24.1 Differential diagnosis of petechial hemorrha
ge — non-palpable, non-retiform and ≤4 mm in diameter. *Partial
list.
24FT2.jpg|Table 24.2 Differential diagnosis for macular purpura a
nd ecchymoses — non-palpable and non-retiform. *Partial list.
24FT3.jpg|Table 24.3 Inflammatory purpura: lesions with prominent
early erythema. HSP, Henoch Schölein purpura; LE, lupus erythematosus;
RA, rheumatoid arthritis.
24FT4.jpg|Table 24.4 Differential diagnosis of non-inflammatory r
etiform purpura (minimal to no erythema in early lesions). DIC, disseminated
intravascular coagulation. *Partial list.

24FT5.jpg|Table 24.5 Differential diagnosis of mixed retiform and
inflammatory morphology.
25FF1.jpg|Fig. 25.1 Cutaneous microvascular occlusion syndr
omes.
25FF2.jpg|Fig. 25.2 Heparin necrosis at site of subcutaneou
s heparin injection. Note branching or retiform pattern of intense hemorrhag
e or necrosis in the center of lesion. From Robson K, Piette W. Adv Dermatol. 19
99;15:153–82, used with permission.
25FF3.jpg|Fig. 25.3 Type I cryoglobulinemia in a patient wi
th multiple myeloma. Note the retiform purpura (A) and the areas of n
ecrosis with the purpuric areas (B). Courtesy of Jean Bolognia, M.D.
25FF4.jpg|Fig. 25.4 Cholesterol emboli. Several irregul
arly shaped ulcers with eschars surrounded by retiform purpura. Courtesy of Kalm
an Watsky, M.D.
25FF5.jpg|Fig. 25.5 Cholesterol emboli. Livedo reticula
ris is seen proximally on the thigh (A); both livedo reticularis and reti
form purpura are seen distally (B).
25FF6.jpg|Fig. 25.6 Retiform purpura of coumadin necrosis. The breast is a characteristic site. From Robson K, Piette W. Adv Dermatol.
1999;15:153–82, used with permission.
25FF7.jpg|Fig. 25.7 Antiphospholipid antibody syndrome.
Purpura and ischemia of the distal portion of the foot. The purpuric lesions ha
ve irregular borders. Courtesy of Jean Bolognia, M.D.
25FF8.jpg|Fig. 25.8 Antiphospholipid antibody syndrome.
Atrophie blanche-like scarring in a lupus patients with APLS.
25FF9.jpg|Fig. 25.9 Livedoid vasculopathy. Punched-out
ulcers are seen on the ankle as well as multiple purpuric macules. (A) Bl
and thrombi are seen in the dermal blood vessels (B).
25FT1.jpg|Table 25.1 Differential diagnosis of cutaneous mi
crovascular occlusion based on pathophysiology. DIC, disseminated intravascu
lar coagulation.
25FT2.jpg|Table 25.2 Basic screening tests for occlusive sy
ndromes. TTP, thrombotic thrombocytopenic purpura; HUS, hemolytic uremic syn
drome.
25FT3.jpg|Table 25.3 International Consensus Statement &#82
11; preliminary criteria for antiphospholipid antibody syndrome42. Definite diagnosis requires at least one clinical and one laboratory criterion
.
25FT4.jpg|Table 25.4 Cutaneous findings in patients with th
e antiphospholipid antibody syndrome.
26FF1.jpg|Fig. 26.1 Cutaneous small vessel vasculitis (CSVV). A Classic purpuric papules and plaques on the lower leg. B CSVV evolving
to form confluent hemorrhagic plaque on the posterior ankle. C Lesions i
n various stages of evolution on the lower leg: petechiae, vesicles, hemorrhagic
plaques and focal necrosis.
26FF2.jpg|Fig. 26.2 Cutaneous small vessel vasculitis (CSVV).
Histology of cutaneous small vessel vasculitis (CSVV) showing angiocentric segm
ental inflammation, endothelial swelling, neutrophilic infiltrate with leukocyto
clasia, and fibrinoid necrosis of blood vessel walls.
26FF3.jpg|Fig. 26.3 Henoch–Schönlein purpura. A Pu
rpuric papules, vesicles, urticarial plaques, and foci of necrosis on the lower
leg. Note the different stages of evolving lesions indicating recurrent crops as
well as post-inflammatory hyperpigmentation after resolution. B Multiple
confluent purpuric papules and plaques grouped on the dorsal foot, ankle, and s
hin. Note central necrosis of some lesions. C Discrete purpuric papules s
urrounding the umbilicus. D Numerous confluent purpuric vesiculopapules o
n the buttocks.
26FF4.jpg|Fig. 26.4 Erythema elevatum diutinum. A Multiple sy
mmetric red-brown nodules and plaques on the extensor surface of the digits. 
B Red-brown plaques and nodules of the concha, antihelix and of the ear.
26FF5.jpg|Fig. 26.5 Erythema elevatum diutinum. A Histology o
f an early stage lesion, demonstrating a dense perivascular infiltrate of neutro
phils admixed with lymphocytes and histiocytes. In addition, this specimen demon
strates scattered nuclear dust and red blood cell extravasation. B Histol
ogy of a late-stage lesion, demonstrating a minimal inflammatory infiltrate and
marked perivascular fibrous thickening.
26FF6.jpg|Fig. 26.6 Acute hemorrhagic edema of childhood. Mul
tiple erythematous, nummular and targetoid plaques on an infant's thighs. Courte
sy of Dr Mary Spraker, Emory University School of Medicine.
26FF7.jpg|Fig. 26.7 Urticarial vasculitis. Several erythemato
us urticarial plaques on the foot and ankle.
26FF8.jpg|Fig. 26.8 Cryoglobulinemia. A Petechiae and purpuri
c plaques on the dorsal foot and the distal aspect of toes. B Confluent p
etechiae and purpuric papules and plaques on the dorsal hand and distal fingers;
note subungual petechiae.
26FF9.jpg|Fig. 26.9 Microscopic polyangiitis. A Petechiae and
multiple purpuric papules with central necrosis on the plantar surface. B Confluent hemorrhagic plaques on the medial and plantar aspect of the foot.
26FF10.jpg|Fig. 26.10 Churg–Strauss syndrome. Crusted,
firm papules of the elbow. Courtesy of Kalman Watsky, M.D.
26FF11.jpg|Fig. 26.11 Wegener's granulomatosis. A Purpuric pl
aques on the distal fingers. B Ulceration of the tongue. Courtesy of Dr T
homas J Lawley, Emory University School of Medicine.
26FF12.jpg|Fig. 26.12 Kawasaki disease. A Diffuse erythematou
s macules and papules on the trunk and confluent erythema of the axilla.
26FT1.jpg|Table 26.1 American College of Rheumatology classificat
ion of vasculitis 19904.
26FT2.jpg|Table 26.2 Chapel Hill consensus classification.
26FT3.jpg|Table 26.3 Physical examination findings leading to sus
picion of vasculitis.
26FT4.jpg|Table 26.4 Laboratory evaluation in known or suspected
vasculitis.
26FT5.jpg|Table 26.5 Invasive diagnostic studies for selected pat
ients with vasculitis.
26FT6.jpg|Table 26.6 Common therapies for vasculitis. 1, doub
le-blind randomized controlled trial; 2, case series; 3, anecdotal reports.
27FF1.jpg|Fig. 27.1 Evaluation of adult patients with eosinophili
c dermatoses. Histologically, these dermatoses are characterized by a promin
ent eosinophilic infiltrate.
27FF2.jpg|Fig. 27.2 Eosinophils. Note the red granules within
the cytoplasm. Courtesy of Ron Rapini M.D.
27FF3.jpg|Fig. 27.3 Granuloma faciale. Red-brown plaque on th
e face. Note the prominent follicular openings. Courtesy of Yale Residents Slide
Collection.
27FF4.jpg|Fig. 27.4 Granuloma faciale. A Dense diffuse dermal
infiltrate with a Grenz zone. B Higher power view of polymorphous infilt
rate of lymphocytes, eosinophils, neutrophils, and plasma cells. Courtesy of Ron
Rapini, M.D.
27FF5.jpg|Fig. 27.5 Wells' syndrome. Erythematous nodules and
plaques. Note the arcuate configuration. Courtesy of Yale Residents Slide Colle
ction.
27FF6.jpg|Fig. 27.6 A Wells' syndrome. Dense dermal inflammat
ion with papillary dermal edema. Note the flame figures in the dermis. In this e
xample there is spongiosis and vesicle formation. B Higher power view of
flame figures in the dermis. Courtesy of Ron Rapini M.D.
27FT1.jpg|Table 27.1 Eosinophilic dermatoses.
28FF1.jpg|Fig. 28.1 Non-infectious neutrophilic dermatoses. E
ntities in the darker box are discussed in this chapter.
28FF2.jpg|Fig. 28.2 Classic lesions of Sweet's syndrome. Eryt
hematous plaques on the forearm.

28FF3.jpg|Fig. 28.3 Sweet's syndrome. Markedly edematous lesi
ons on the upper back. Courtesy of Kalman Watsky, M.D.
28FF4.jpg|Fig. 28.4 Sweet's syndrome. Multiple edematous and
crusted papules and plaques. Courtesy of Kalman Watsky, M.D.
28FF5.jpg|Fig. 28.5 Sweet's syndrome. Obvious erythema of the
sclera in a patient with ocular involvement. Courtesy of Kalman Watsky, M.D.
28FF6.jpg|Fig. 28.6 Histologic features of Sweet's syndrome.
Papillary dermal edema, and a dense diffuse dermal infiltrate of primarily neutr
ophils. Courtesy of Ron Rapini, M.D.
28FF7.jpg|Fig. 28.7 Pathergy in a patient with pyoderma gangrenos
um. The lesion appeared at the site of an intravenous catheter.
28FF8.jpg|Fig. 28.8 Classic ulcerative pyoderma gangrenosum. A In this patient with chronic ulcerative colitis, the ulcers on the skin have a
n undermined gunmetal gray border. B In addition to an overhanging border
, this deep ulceration on the elbow has a purulent base.
28FF9.jpg|Fig. 28.9 The earliest clinical lesion in pyoderma gang
renosum is a pustule with an inflammatory base. This patient had Crohn's dis
ease.
28FF10.jpg|Fig. 28.10 Bullous pyoderma gangrenosum. This pati
ent had ulcerative colitis.
28FF11.jpg|Fig. 28.11 Variant pyoderma vegetans. A Pyostomati
tis vegetans in patient with ulcerative colitis. B Pyoderma vegetans foll
owing trauma to skin.
28FF12.jpg|Fig. 28.12 Pyoderma gangrenosum. Diffuse neutrophi
ls are present at the base of an ulceration. Courtesy of Ron Rapini, M.D.
28FF13.jpg|Fig. 28.13 Behçet's disease: mucocutaneous lesion
s. A Oral aphthosis. B Perianal aphthosis.
28FF14.jpg|Fig. 28.14 Behçet's disease: systemic involvement
. A Iritis and cutaneous pustular vasculitis. B Superficial migratory
thrombophlebitis.
28FF15.jpg|Fig. 28.15 Bowel-associated dermatosis–arthritis
syndrome. Lesions of erythema nodosum and small vessel vasculitis.
28FT1.jpg|Table 28.1 Systemic manifestations of Sweet’s syn
drome.
28FT2.jpg|Table 28.2 Criteria for diagnosis of Sweet’s synd
rome. Two major and two minor criteria are needed for the diagnosis.
28FT3.jpg|Table 28.3 The differential diagnosis of Sweet’s
syndrome.
28FT4.jpg|Table 28.4 Approach to the patient with a hematologic m
alignancy and associated neutrophilic dermatoses. IBD, inflammatory bowel di
sease. *Usually in setting of chemotherapy. **May be lymphocytic in setting of c
hemotherapy-induced neutropenia.
28FT5.jpg|Table 28.5 Histopathology of pyoderma gangrenosum: case
study results.*The Wake Forest University School of Medicine/University of
Louisville series: 104 biopsies13.
28FT6.jpg|Table 28.6 Evaluation of a patient with pyoderma gangre
nosum.
28FT7.jpg|Table 28.7 The differential diagnosis of pyoderma gangr
enosum.
28FT8.jpg|Table 28.8 Therapeutic ladder for the treatment of pyod
erma gangrenosum. 1, double-blind study; 2, case series; 3, anecdotal report
. *The common initial dose is 60–120 mg PO qd.
28FT9.jpg|Table 28.9 Neutrophilic dermatoses associated with bowe
l disorders.
28FT10.jpg|Table 28.10 International Study Group criteria for the
diagnosis of Behçet’s disease27.
28FT11.jpg|Table 28.11 Treatment of Behçet’s disease<s
up>30. 1, double-blind study; 2, case series; 3, anecdotal report.
29FF1.jpg|Fig. 29.1 Gestational pemphigoid. Urticarial papule
s with central crusts.

29FF2.jpg|Fig. 29.2 Gestational pemphigoid. Direct IF demonst
rating deposits of C3 along the dermo-epidermal junction. Courtesy of Ron Rapini
, M.D.
29FF3.jpg|Fig. 29.3 Pruritic urticarial papules and plaques of pr
egnancy. The edematous urticarial lesions favor the striae (A) and th
e upper thighs (B) and spare the umbilicus.
egnancy. The urticarial lesions favor the striae (A) and thighs (B
) but spare the umbilicus.
egnancy. Urticarial lesions as well as pseudovesicles on the hand.
29FF6.jpg|Fig. 29.6 Pruritic folliculitis of pregnancy. Extre
mely pruritic follicular papules and pustules, the majority of which have been e
xcoriated. Cultures were negative and liver-function tests and serum and bile ac
id levels were normal. Courtesy of Jean Bolognia, M.D.
29FF7.jpg|Fig. 29.7 Evaluation of a pregnant patient with pruritu
s ± prurigo nodularis.
29FF8.jpg|Fig. 29.8 Palmar erythema of pregnancy.
29FT1.jpg|Table 29.1 Historical classification of the dermatoses
of pregnancy.
29FT2.jpg|Table 29.2 Working classification of the pruritic entit
ies of pregnancy. *Preferred terminology. #Considered by some authors to be
a separate entity.
29FT3.jpg|Table 29.3 Dermatoses of pregnancy – fetal risk a
nd involvement of newborn skin.
29FT4.jpg|Table 29.4 Physiologic changes during pregnancy. Mo
dified from Kroumpouzos & Cohen28.
30FF1.jpg|Fig. 30.1 Four major ultrastructural subregions of epid
ermal basement membrane. The four major ultrastructural subregions of the ep
idermal basement membrane consist of the cytoskeleton, hemidesmosomal plaques an
d plasma membranes of basal keratinocytes; the electron lucent lamina lucida; th
e lamina densa; and the sublamina densa region of the papillary dermis.
30FF2.jpg|Fig. 30.2 ‘Laminated’ model of the epiderma
l basement membrane. In the laminated model, keratin intermediate filaments
attach to electron-dense hemidesmosomes on the basal plasma membranes of keratin
ocytes. Hemidesmosomes connect to the underlying lamina densa (or basement membr
ane proper) by small thread-like strands termed anchoring filaments. The lamina
densa and the overlying epidermis are tethered to the papillary dermis by anchor
ing fibrils, a series of looping elements along the underside of the lamina dens
a that serve as attachment sites for fibrillar proteins in the papillary dermis.
30FF3.jpg|Fig. 30.3 Interactions of selected molecules within the
epidermal basement membrane. These interactions promote epidermal adhesion
and also play a key role in a number of dermatologic diseases. Important molecul
ar interactions include those between: (1) plakin family members, BPAG1 and plec
tin, with keratin intermediate filaments; (2) the former with BPAG2 and integrin
α6β4 (specifically, the large cytoplasmic domai
n of integrin subunit β4); (3) the cytoplasmic domains of BPAG2
and integrin subunit β4; (4) the extracellular domains of BPAG2
and integrin subunit α6; (5) integrin α6β<s
ub>4 in hemidesmosomes and laminin 5 in the lamina densa; (6) laminin 5 an
d type VII collagen; (7) type VII collagen with type IV collagen, fibronectin, a
nd type I collagen in the sublamina densa region. While BPAG2 is thought to bind
to laminin 5, this association is yet to be demonstrated formally.
30FF4.jpg|Fig. 30.4 Type IV collagen. The schematic depicts a
monomer, a tetramer ‘spider’ and a lattice. The latter results from
the aggregation of type IV collagen molecules.
30FF5.jpg|Fig. 30.5 Autoantigens in selected autoimmune bullous d
iseases. The approximate localization of major autoantigens in selected sube
pidermal immunobullous diseases. AECP, antiepiligrin cicatricial pemphigoid; BP,
bullous pemphigoid; BSLE, the bullous eruption of systemic lupus erythematosus;

CP, cicatricial pemphigoid; EBA, epidermolysis bullosa acquisita; LAD, linear I
gA dermatosis; PG, pemphigoid gestationis.
30FF6.jpg|Fig. 30.6 Cleavage plane in salt-split skin. Schema
tic overview of the cleavage plane in 1 M salt-split skin.
30FF7.jpg|Fig. 30.7 Common localization of autoantibodies in indi
rect immunofluorescence microscopy studies of salt-split skin. Subregions of
1 M salt-split skin commonly bound by circulating autoantibodies from pati
ents with subepidermal immunobullous diseases.
30FF8.jpg|Fig. 30.8 Cleavage planes in epidermolysis bullosa.
30FT1.jpg|Table 30.1 Representative adhesion proteins in the epid
ermal basement membrane.
30FT2.jpg|Table 30.2 Targets common to autoimmune and inherited b
listering diseases. BP, bullous pemphigoid; CP, cicatricial pemphigoid; EB,
epidermolysis bullosa; HD, hemidesmosome; PG, pemphigoid gestationis.
30FT3.jpg|Table 30.3 Well-characterized subepidermal immunobullou
s diseases.
30FT4.jpg|Table 30.4 Localization of immunoreactants in immunoflu
orescence microscopy studies of 1 M salt-split skin. CP, cicatricial pemphig
oid. *See Schmidt & Zillikens for specific information about these incomplet
ely characterized immunobullous diseases. †These studies utilize patient s
kin after it is split with 1 M NaCl.
30FT5.jpg|Table 30.5 Forms of epidermolysis bullosa. EB, epid
ermolysis bullosa.
31FF1.jpg|Fig. 31.1 Indirect immunofluorescence of pemphigus sera
with normal human epidermis as a substrate. The hallmark of pemphigus is th
e finding of IgG autoantibodies directed against the cell surface of keratinocyt
es. A Pemphigus vulgaris sera containing anti-desmoglein 3 IgG alone
stain the cell surfaces in the lower epidermis. B Pemphigus vulgaris ser
a containing both anti-desmoglein 3 IgG and anti-desmoglein 1 IgG stai
n the cell surfaces throughout the epidermis. C Pemphigus foliaceus sera,
which contain only anti-desmoglein 1 IgG, stain the cell surfaces througho
ut the epidermis, but more intensely in the superficial layers.
31FF2.jpg|Fig. 31.2 Molecular structure of the pemphigus antigens
. The extracellular (EC) region has five cadherin repeats, which have calciu
m-binding motifs. The intracellular cadherin-specific (ICS) domain is well conse
rved among cadherins and it is responsible for interactions with β-catenin
or plakoglobin. Desmogleins have their own unique sequences of 29 ± 1 resid
ues (repeating unit domain or RUD). Each desmocollin isotype has two products (a
and b) derived from alternatively spliced transcripts of a single gene.
31FF3.jpg|Fig. 31.3 The adherens junction and desmosome. A Th
e adherens junction complex contains classic cadherins as transmembrane constitu
ents and α-catenins, β-catenins, and plakoglobin as cytoplasmic consti
tuents. A classic cadherin is directly coupled through its cytoplasmic tail to &
#946;-catenin or plakoglobin, which in turn is linked to α-catenin, which b
inds to actin. B The desmosome complex includes desmogleins and desmocoll
ins as transmembrane constituents, and plakoglobin, plakophilin, and desmoplakin
as cytoplasmic constituents. Desmogleins and desmocollins associate with plakog
lobin, which in turn binds to desmoplakin, which links keratin to the membrane.
31FF4.jpg|Fig. 31.4 Logical explanation for the localization of b
lister formation in classic pemphigus by desmoglein compensation theory. The
colored triangles represent the distribution of desmoglein 1 (Dsg1) and desmogl
ein 3 (Dsg3) in the skin (A) and mucous membranes (B). Pemphigus f
oliaceus sera contain only anti-Dsg1 IgG, which causes superficial blisters in t
he skin because Dsg3 functionally compensates for the impaired Dsg1 in the lower
part of the epidermis (A1), whereas those antibodies do not cause bliste
rs in the mucous membranes because cell–cell adhesion is mainly mediated b
y Dsg3 (B1). Sera containing only anti-Dsg3 IgG cause no or only limited
blisters in the skin because Dsg1 compensates for the loss of Dsg3-mediated adhe
sion (A2), however, these sera induce separation in the mucous membranes
where the low expression of Dsg1 will not compensate for the loss of Dsg3-mediat
ed adhesion (B2). When sera contain both anti-Dsg1 and anti-Dsg3 IgG, the
function of both Dsgs is compromised and blisters occur in both the skin and mu
cous membranes (A3, B3). In neonatal skin, the situation is similar to th
at shown here for mucous membranes.
31FF5.jpg|Fig. 31.5 Pemphigus vulgaris. A Essentially all pat
ients develop painful oral mucosal erosions. B Flaccid blisters, crusts,
and macular erythema. Courtesy of Dr Ronald Rapini. C In a severe case, a
large area of the back is affected, leading to a loss of body fluids and second
ary bacterial infections. Courtesy of Department of Dermatology, Hamamatsu Unive
rsity School of Medicine.
31FF6.jpg|Fig. 31.6 Pemphigus vegetans. Extensive vegetating
granulomatous lesions are noted.
31FF7.jpg|Fig. 31.7 Pemphigus foliaceus. A The scaly, crusted
erosions are widely distributed on the upper back. B A typical lesion of
pemphigus foliaceus is a scaly crusted erosion because the vesicles are fragile
and rupture easily.
31FF8.jpg|Fig. 31.8 Pemphigus erythematosus. Scaly crusted er
osions are seen on the malar area of the face.
31FF9.jpg|Fig. 31.9 Paraneoplastic pemphigus. The characteris
tic clinical feature is severe intractable stomatitis that extends onto the verm
ilion lip.
31FF10.jpg|Fig. 31.10 IgA pemphigus. A Subcorneal pustular de
rmatosis (SPD) type. Pustules tend to coalesce to form an annular or circinate p
attern with crusts present centrally. B Intraepidermal neutrophilic (IEN)
type. The characteristic sunflower-like configuration of pustules is seen.
31FF11.jpg|Fig. 31.11 Histology of pemphigus vulgaris. A Blis
ters in the skin show suprabasilar acantholysis with a few acantholytic cells in
the blister cavity. B The border of a blister on the buccal mucosa shows
intraepithelial separation in the lower part of the mucosal epithelia.
31FF12.jpg|Fig. 31.12 Histology of pemphigus foliaceus. Cleft
ing is seen in the upper spinous layer of the epidermis with several acantholyti
c cells detaching from the roof of the blister.
31FF13.jpg|Fig. 31.13 Histology of paraneoplastic pemphigus.
Suprabasilar acantholysis is seen along with a combination of basal cell vacuola
r change, necrotic keratinocytes, and lymphocytes within the epidermis.
31FF14.jpg|Fig. 31.14 Histology of IgA pemphigus. Intraepider
mal subcorneal pustule with numerous neutrophils is seen subcorneally in the SPD
type (A), and in the mid stratum spinosum in the IEN type (B).
31FT1.jpg|Table 31.1 Classification of pemphigus.
31FT2.jpg|Table 31.2 Target antigens in pemphigus.
31FT3.jpg|Table 31.3 Causes of eosinophilic spongiosis.
31FT4.jpg|Table 31.4 Therapeutic ladder for pemphigus vulgaris.
32FF1.jpg|Fig. 32.1 Potential mechanisms of blister formation in
bullous pemphigoid.
32FF2.jpg|Fig. 32.2 Bullous pemphigoid. A Urticarial, infiltr
ated, and annular erythematous plaques on the trunk and abdomen. B Genera
lized eruption with blisters and erosions eroded and crusted lesions in the same
patient later in the course of the disease.
32FF3.jpg|Fig. 32.3 Bullous pemphigoid. A Excoriated eczemato
us lesions on the forearm. B Confluent plaques with tense blisters in the
inguinal area and inner aspect of the legs in the same patient.
32FF4.jpg|Fig. 32.4 Bullous pemphigoid. A and B Eczema
tous, slightly infiltrated lesions on the trunk. C Dyshidrotic lesions on
the palm with confluent vesicles and bullae. D Prurigo nodularis like-le
sions on the arm.
32FF5.jpg|Fig. 32.5 Childhood bullous pemphigoid. A Generaliz
ed bullous and crusted lesions. B Vulvar bullous pemphigoid.
32FF6.jpg|Fig. 32.6 Bullous pemphigoid. Subepidermal blister
formation and an inflammatory infiltrate composed of neutrophils and eosinophils

in the dermis and bulla cavity, by light microscopy. Inset, at higher power, sh
ows the infiltrate rich in eosinophils (hematoxylin–eosin stain). The same
pattern of labeling is observed in patients with cicatricial pemphigoid.
32FF7.jpg|Fig. 32.7 Bullous pemphigoid. A Direct immunofluore
scence microscopy studies of perilesional skin demonstrating linear continuous d
eposits of IgG along the epidermal basement membrane zone (arrow). The same patt
ern of labeling is observed in cicatricial pemphigoid and epidermolysis bullosa
acquisita. B Indirect immunofluorescence microscopy study utilizing saltsplit normal human skin as a substrate. Patient's IgG autoantibodies are bound t
o the epidermal side (roof) of the split (arrow). The level of the artificial se
paration is indicated by asterisk. Cell nuclei are stained blue. The same patter
n of labeling is observed in a subset of patients with cicatricial pemphigoid.
32FF8.jpg|Fig. 32.8 Bullous pemphigoid. Indirect immunoelectr
on microscopy study in which autoantibodies directed against BP230 specifically
label the hemidesmosomal plaque of the hemidesmosomal adhesion complex (gold lab
eling = black dots). BK, basal keratinocyte; LD, lamina densa. Kindly provided b
y Prof. H. Shimizu, Hokkaido University of Sapporo, Japan.
32FF9.jpg|Fig. 32.9 Bullous pemphigoid: reactivity of serum with
BP180 and BP230. A Immunoprecipitation studies of utilizing radiolabeled hum
an keratinocyte extracts: lanes 1–3, serum samples from BP patients immuno
precipitate proteins of 230 kDa (BP230) and 180 kDa (BP180). Lane 4, r
eactivity of normal human serum. B Immunoblot studies of keratinocyte ext
racts: lane 1, reactivity of monoclonal antibodies directed against BP230; lane
2, reactivity of monoclonal antibodies directed against BP180; lane 3, reactivit
y of a BP serum sample with a protein of approximately 230 kDa; lane 4, rea
ctivity of a normal human serum. C Reactivity with the extracellular doma
in of BP180, which was expressed by transfection of COS-7 cells: lanes 1 to 3: s
erum samples from BP patients.
32FF10.jpg|Fig. 32.10 Bullous pemphigoid: reactivity of serum wit
h BP180. Enzymelinked immunosorbent assay (ELISA) utilizing eukaryotic-expre
ssed recombinant protein consisting of the ectodomain of BP18029. Rea
ctivity with serum samples obtained from patients with bullous pemphigoid (BP),
gestational pemphigoid (GP), pemphigus (PE) and normal human subjects (NHS). The
cut-off for the ELISA was equal to the mean value of the negative control serum
samples +1 standard deviation.
32FF11.jpg|Fig. 32.11 Cicatricial pemphigoid. Erosions of the
gingival margins (desquamative or erosive gingivitis).
32FF12.jpg|Fig. 32.12 Cicatricial pemphigoid. Chronic erosion
s on the hard palate.
32FF13.jpg|Fig. 32.13 Cicatricial pemphigoid. Typical ocular
involvement as manifested by symblepharon.
32FF14.jpg|Fig. 32.14 Cicatricial pemphigoid. Cutaneous invol
vement of the scalp with scarring and atrophy resulting in alopecia.
32FF15.jpg|Fig. 32.15 Cicatricial pemphigoid. Indirect immuno
electron microscopy. Immune deposits (peroxidase labeling) are localized to the
lamina densa (LD) and the lower lamina lucida.
32FF16.jpg|Fig. 32.16 Epidermolysis bullosa acquisita. Milia
and scarring on the dorsum of the hand in association with skin fragility. Court
esy of Dr C Prost, University Hospital Saint-Louis, Paris, France.
32FF17.jpg|Fig. 32.17 Epidermolysis bullosa acquisita. Bullou
s and erosive lesions in a patient with multiple myeloma.
32FF18.jpg|Fig. 32.18 Epidermolysis bullosa acquisita. Multip
le erosions of the palate reminiscent of cicatricial pemphigoid. Courtesy of Dr
C. Prost, University Hospital Saint-Louis, Paris, France.
32FF19.jpg|Fig. 32.19 Epidermolysis bullosa acquisita. Indire
ct immunoelectron microscopy. Labeling of immunogold particles (arrow) along the
anchoring fibrils present below the lamina densa (LD).
32FT1.jpg|Table 32.1 Major autoantigens of subepidermal autoimmun
e-mediated blistering diseases.
32FT2.jpg|Table 32.2 Survey of controlled trials for the treatmen

t of patients with bullous pemphigoid.
33FF1.jpg|Fig. 33.1 Gluten-sensitive enteropathy.
33FF2.jpg|Fig. 33.2 Iodine and dapsone and their effects on derma
titis herpetiformis.
33FF3.jpg|Fig. 33.3 Dermatitis herpetiformis. Erythematous pa
pulovesicles on the elbows.
33FF4.jpg|Fig. 33.4 Dermatitis herpetiformis. Erythematous pa
pules on the knees.
33FF5.jpg|Fig. 33.5 Dermatitis herpetiformis. Neutrophilic mi
croabscess. Courtesy of Ron Rapini, M.D.
33FF6.jpg|Fig. 33.6 Dermatitis herpetiformis. Direct immunofl
uorescence showing granular IgA deposition along the dermal–epidermal junc
tion.
33FF7.jpg|Fig. 33.7 Linear IgA bullous dermatosis. Bullae ero
sions and erythematous patches of LABD. Note the peripheral locations of blister
s in some areas.
33FF8.jpg|Fig. 33.8 Linear IgA bullous dermatosis. The circum
ferential and linear vesicles and bullae are typical of LABD.
33FF9.jpg|Fig. 33.9 Linear IgA bullous dermatosis. Direct imm
unofluorescence showing the linear pattern of IgA depositions.
33FF10.jpg|Fig. 33.10 Cleavage ectodomains of BPAG2.
33FF11.jpg|Fig. 33.11 Linear IgA bullous dermatosis. Annular
vesicopustules due to vancomycin-induced LABD.
33FF12.jpg|Fig. 33.12 Linear IgA bullous dermatosis. Annular
and polycyclic plaques of the trunk in two women with LABD.
33FT1.jpg|Table 33.1 Dermatitis herpetiformis – historic la
ndmarks.
33FT2.jpg|Table 33.2 Autoimmune disorders associated with dermati
tis herpetiformis.
33FT3.jpg|Table 33.3 Characteristics that differentiate DH, LABD
and BP.
33FT4.jpg|Table 33.4 Side effects of dapsone. *In decreasing
order of frequency.
33FT5.jpg|Table 33.5 Drug-induced linear IgA bullous dermatosis.
34FF1.jpg|Fig. 34.1 Ultrastructral sites of blister formation in
major forms of epidermolysis bullosa. A Ultrastructural sites of blister for
mation in three subtypes of EB simplex. The ultrastructure of normal intact skin
is presented for comparison. In all three major subtypes of EBS (WC, K, and DM)
, blisters arise within the lowermost intracytoplasmic portion of the basilar ke
ratinocyte. In one subtype, EBS-DM, keratin filaments tend to coalesce into larg
er electron-dense clumps. B Ultrastructural sites of blister formation in
two major subtypes of junctional EB. All forms of JEB are characterized by blis
ter formation within the lamina lucida of the dermo–epidermal junction. As
such, the lamina densa remains firmly attached to the dermis which forms the ba
se of the blister cavity. Subbasal dense plates and anchoring filaments are abse
nt in both subtypes of JEB. Hemidesmosomes are absent in JEB-H, whereas they are
reduced in number and appear rudimentary in structure within skin from patients
with the JEB-nH subtype. C Ultrastructural sites of blister formation in
three major subtypes of dystrophic EB. Blister formation occurs beneath the lam
ina densa in all forms of dystrophic EB. Whereas anchoring fibrils appear normal
in size and structure in DDEB skin, they may be somewhat reduced in number. Con
sistent with the presence of sublamina densa cleavage, these anchoring fibrils r
emain attached to the blister roof, which is composed of intact epidermis and an
attached basement membrane (that includes the lamina densa). In contrast, ancho
ring fibrils are completely absent in lesional skin from patients with RDEB-HS.
If detectable in RDEB-nHS skin, they are both markedly reduced in number and rud
imentary in appearance.
34FF2.jpg|Fig. 34.2 Epidermolysis bullosa simplex, Weber–Co
ckayne. Bullae arising on the toes (A) and the plantar surface (A,
B) at sites of lateral or rotary traction.
34FF3.jpg|Fig. 34.3 Dominant dystrophic epidermolysis bullosa. Erosions, scarring and milia of the digits (A,B) as well as partial she
dding of a toenail (B). A discrete area of scarring on the elbow with bli
sters, crusting and milia (C).
34FF4.jpg|Fig. 34.4 Increasing frequency of specific cutaneous fi
ndings, from localized EB simplex to RDEB.
34FF5.jpg|Fig. 34.5 Helpful cutaneous findings in patients with e
pidermolysis bullosa.
34FF6.jpg|Fig. 34.6 Epidermolysis bullosa simplex, Dowling–
Meara. Small clustered vesicles in an arcuate array on the shoulder in this
child.
34FF7.jpg|Fig. 34.7 Epidermolysis bullosa simplex, Dowling–
Meara. Diffuse keratoderma of the palm in an adult.
34FF8.jpg|Fig. 34.8 Junctional epidermolysis bullosa, Herlitz. Blisters on the elbow and large areas of denuded skin; note the bright red col
or in the axilla and groin. Courtesy of Yale Residents Slide Collection.
34FF9.jpg|Fig. 34.9 Recessive dystrophic epidermolysis bullosa, H
allopeau–Siemens. Note the partial mitten deformities of the hands in
this child.
34FF10.jpg|Fig. 34.10 Ultrastructure of epidermolysis bullosa sim
plex, junctional epidermolysis bullosa and recessive dystrophic epidermolysis bu
llosa. A EM of an induced blister in EB simplex (in this case Weber–Co
ckayne variant) demonstrates skin cleavage (asterisk) within the inferior-most p
ortion of the basilar keratinocyte. B EM of a spontaneous blister from a
patient with the Herlitz subtype of junctional EB reveals skin cleavage (asteris
ks) within the lamina lucida. Hemidesmosomes, sub-basal dense plates and anchori
ng filaments are all absent, diagnostic of Herlitz disease. In contrast, anchori
ng fibrils are still present in normal amounts within the underlying dermis. 
C EM of the roof of a spontaneous blister from a patient with RDEB, Hallopea
u–Siemens reveals cleavage (asterisks) beneath the level of the lamina den
sa. Anchoring fibrils are absent along the epidermal roof of the blister, diagno
stic of severe generalized RDEB.
34FT1.jpg|Table 34.1 Epidermolysis bullosa types and their associ
ated target proteins, structures and level of cleavage. EBS, EB simplex; EBS
S, EBS superficialis; EBS-MD, EBS with muscular dystrophy; JEB, junctional EB; J
EB-PA, JEB with pyloric atresia; DDEB, dominant dystrophic EB; RDEB, recessive d
ystrophic EB.
34FT2.jpg|Table 34.2 Currently accepted major and minor epidermol
ysis bullosa types and subtypes. Previously referred to as generalized atrop
hic benign EB.
34FT3.jpg|Table 34.3 Ultrastructural findings in inherited epider
molysis bullosa. EBS, EB simplex; EBS-WC, EBS, Weber–Cockayne; EBS-DM,
EBS, Dowling–Meara; EBS-MD, EBS with muscular dystrophy; EBS-AR, autosoma
l recessive EBS; EBSS, EBS superficialis; JEB-H, JEB, Herlitz; JEB-nH, JEB, nonHerlitz; JEB-PA, JEB with pyloric atresia; DDEB, dominant dystrophic EB; RDEB, r
ecessive dystrophic EB; RDEB-HS, RDEB, Hallopeau–Siemens; RDEB-nHS, RDEB,
non-Hallopeau–Siemens; HD, hemidesmosome; SBDP, sub-basal dense plate; AF,
anchoring fibrils; DDEBTBDN, DDEB, transient bullous dermolysis of the newborn.
34FT4.jpg|Table 34.4 Genodermatoses associated (at least transien
tly) with blisters, especially during the newborn period.
35FF1.jpg|Fig. 35.1 Bullosis diabeticorum. Tense blisters on
the palm.
35FF2.jpg|Fig. 35.2 Bullae in an area of pressure in a previously
comatose patient.
35FF3.jpg|Fig. 35.3 Neurologic blisters. Tense blisters on th
e dorsum of the hand on the hemiplegic side of a patient with a past cerebrovasc
ular accident.
35FF4.jpg|Fig. 35.4 Bullous variant of small vessel vasculitis.
35FF5.jpg|Fig. 35.5 Exaggerated bullous reaction to insect bites
in a patient with chronic lymphocytic leukemia.
35FF6.jpg|Fig. 35.6 Serohemorrhagic blisters in the setting of an
acute exacerbation of chronic lymphedema.
35FF7.jpg|Fig. 35.7 Approach to the patient with bland bullae of
the distal lower extremities.
35FT1.jpg|Table 35.1 Differential diagnosis of vesiculobullous di
sease.
36FF1.jpg|Fig. 36.1 Erythema toxicum neonatorum. Scattered pa
pulovesicles with an erythematous flare. Courtesy of Kalman Watsky, M.D.
36FF2.jpg|Fig. 36.2 Bullous impetigo. Multiple superficial er
osions with collarettes of scale in the diaper area. Note the scattered pustules
.
36FF3.jpg|Fig. 36.3 Transient neonatal pustular melanosis. Pu
stules, hyperpigmented macules and collarettes of scale are seen on the neck of
an African-American neonate.
36FF4.jpg|Fig. 36.4 Miliaria crystallina. Tiny, superficial v
esicles, seen on the back and neck of this newborn, are characteristic of miliar
ia crystallina. From Eichenfield LF, Frieden IJ, Esterly NB. Textbook of neonata
l dermatology. ©2001 Saunders.
36FF5.jpg|Fig. 36.5 Neonatal cephalic pustulosis. Papulopustu
les on the cheeks of a 1-month old child.
36FF6.jpg|Fig. 36.6 Aplasia cutis congenita. Ulcerations on t
he vertex of the scalp may be misdiagnosed as a herpes simplex virus infection.
The angulated appearance of the larger ulceration would be against HSV.
36FF7.jpg|Fig. 36.7 Acropustulosis of infancy. Multiple vesic
opustules with an erythematous base on the plantar surface.
36FF8.jpg|Fig. 36.8 Incontinentia pigmenti stage I. Multiple
vesicles and bullae with an erythematous border on the lower extremity.
36FF9.jpg|Fig. 36.9 Neonatal herpes simplex virus infection.
Note the clustering of the vesicles on an erythematous base.
36FF10.jpg|Fig. 36.10 Diffuse scaling and a large erosion with sc
ale-crust in a neonate with bullous congenital ichthyosiform erythroderma. H
istologically, epidermolytic hyperkeratosis was seen.
36FF11.jpg|Fig. 36.11 Staphylococcal scalded skin syndrome. R
adiating perioral scale crusts due to exfoliative toxins.
36FF12.jpg|Fig. 36.12 Bullous mastocytosis. Widespread erosio
ns in an infant with diffuse infiltration of the skin with mast cells. Note the
thickened leathery appearance of the skin.
36FT1.jpg|Table 36.1 Differential diagnosis of vesiculopustular d
iseases. KOH, potassium hydroxide examination; DFA, direct fluorescent antib
ody; PCR, polymerase chain reaction; PMN, polymorphonuclear leukocyte; CNS, cent
ral nervous system. Adapted from Frieden IJ, Howard R. In: Eichenfield LF, Fried
en IJ, Esterly NB (eds). Textbook of Neonatal Dermatology. Philadelphia: WB Saun
ders. 2001; 144–6
36FT2.jpg|Table 36.2 Differential diagnosis of bullae, erosions a
nd ulcerations. DFA, direct fluorescent antibody; CNS, central nervous syste
m; DEJ, dermal–epidermal junction; FDP, fibrin degradation product. *One c
ase with neutrophilic infiltrate in the dermis has been reported. Adapted from F
rieden IJ, Howard R. In: Eichenfield LF, Frieden IJ, Esterly NB (eds). Textbook
of Neonatal Dermatology. Philadelphia: WB Saunders. 2001; 147–51
37FF1.jpg|Fig. 37.1 Pilosebaceous unit with apocrine and eccrine
sweat gands. The pilosebaceous unit is shown with an associated apocrine swe
at gland and a nearby eccrine sweat gland.
37FF2.jpg|Fig. 37.2 The eccrine gland. Ultrastructure of the
secretory coil of an eccrine gland with dilated lumen (l), clear or secretory ce
ll (c), dark cells with basophilic granules (b) and myoepithelial cells (m).
37FF3.jpg|Fig. 37.3 The eccrine gland. Ultrastructure of the
ductal epithelium of an eccrine gland demonstrating two or more layers of cuboid
al cells.
37FF4.jpg|Fig. 37.4 Vellus, sebaceous and terminal follicles.
Three different types of pilosebaceous unit. A Vellus follicle with a sm
all sebaceous gland and a short thin hair. B Sebaceous follicle with a la
rge and multilobular sebaceous gland. C Terminal follicle with a thicker
hair. Adapted from ref. 17.
37FF5.jpg|Fig. 37.5 Resident microflora within the pilosebaceous
unit. Localization of resident microflora within the pilosebaceous unit and
electron microscopic view of organisms: A Pityrosporum; B S. epidermidis; C P. acnes.
37FF6.jpg|Fig. 37.6 Sebaceous gland. Electron photomicrograph
of partially differentiated and mature lipid cells of a sebaceous gland.
37FT1.jpg|Table 37.1 Characteristics of sweat glands.
37FT2.jpg|Table 37.2 Innervation and pharmacologic responses of s
weat glands
37FT3.jpg|Table 37.3 Methods for studying sweat production1&
#8211;4
38FF1.jpg|Fig. 38.1 Pathogenesis of acne.
38FF2.jpg|Fig. 38.2 Pathways of C19 steroid metabolism. DHEA
is a weak androgen that is converted to the more potent testosterone by 3βHSD and 17β-HSD. 5α-Reductase then converts testosterone to DHT, the p
redominant hormonal effector on the sebaceous gland. Both DHEA and testosterone
can be metabolized to estrogens by the enzyme aromatase. The sebaceous gland exp
resses each of these enzymes.
38FF3.jpg|Fig. 38.3 Predominantly comedonal acne in a young woman
.
38FF4.jpg|Fig. 38.4 Closed comedones highlighted by side lighting
. Courtesy Ronald Rapini, M.D.
38FF5.jpg|Fig. 38.5 Open comedones in a patient with scarring cys
tic acne. Courtesy of Yale Residents Slide Collection.
38FF6.jpg|Fig. 38.6 Acne vulgaris. Papules, pustules and scattere
d small cysts. Courtesy Kalman Watsky, M.D.
38FF7.jpg|Fig. 38.7 Severe cystic acne, which is best treated wit
h low doses of isotretinoin initially. Courtesy of Yale Residents Slide Coll
ection.
38FF8.jpg|Fig. 38.8 Pitted scarring of the face due to acne (A) a
nd anetoderma-like papular scars of the upper trunk following severe cystic acne
(B). Courtesy of Yale Residents Slide Collection.
38FF9.jpg|Fig. 38.9 Acne fulminans in a patient with ulcerations
and hemorrhagic crusting.
38FF10.jpg|Fig. 38.10 Solid facial edema with obvious soft tissue
swelling in the midline of the face.
38FF11.jpg|Fig. 38.11 Abrupt eruption of follicular papules and p
ustules on the trunk following the administration of high-dose dexamethasone. Courtesy of Yale Residents Slide Collection.
38FF12.jpg|Fig. 38.12 Druginduced acne due to isoniazid. Cour
tesy Kalman Watsky, M.D.
38FF13.jpg|Fig. 38.13 Infantile acne with papulopustules and infl
ammatory cysts on the cheeks. Courtesy Kalman Watsky, M.D.
38FF14.jpg|Fig. 38.14 Inflamed comedone. There is disruption
of the piolsebaceous unit and secondary inflammation. (Courtesy Dr Ronald Rapini
.)
38FF15.jpg|Fig. 38.15 Approach to the patient with treatment-resi
stant acne vulgaris.
38FF16.jpg|Fig. 38.16 Serous crusting due to impetigo in a patien
t treated with isotretinoin.
38FT1.jpg|Table 38.1 Differential diagnosis of acne. *Can als
o lead to rosacea-like picture (see Chapter 39). †Early or small sized. &#
167;In the differential diagnosis of cystic lesions of the trunk.
38FT2.jpg|Table 38.2 History and physical examination of the acne
patient.
38FT3.jpg|Table 38.3 Common therapies for acne vulgaris. 1, D
ouble-blind study; 2, clinical series; 3, anecdotal.
38FT4.jpg|Table 38.4 Topical retinoid preparations used for acne
vulgaris. Preparations that are currently available.
39FF1.jpg|Fig. 39.1 Vascular rosacea. Persistent erythema of
the cheeks in addition to telangiectasias. Courtesy of Kalman Watsky, M.D.
39FF2.jpg|Fig. 39.2 Vascular rosacea. Multiple telangiectasia
s with enhancement in sun-exposed areas. The patient had received oral corticost
eroids on a chronic basis. Courtesy of Ron Rapini, M.D.
39FF3.jpg|Fig. 39.3 Rhinophyma. Obvious nodular enlargement o
f the nose due to sebaceous hyperplasia. Courtesy of Yale Residents Slide Collec
tion.
39FF4.jpg|Fig. 39.4 Phymatous and inflammatory rosacea. Enlar
gement of the nose and cheeks in a patient with granulomatous rosacea.
39FF5.jpg|Fig. 39.5 Inflammatory rosacea. Papular (A)
and papulopustular (B) forms involving the cheeks.
39FF6.jpg|Fig. 39.6 Inflammatory rosacea. Most prominent invo
lvement of the cheeks and nose. Courtesy of Yale Residents Slide Collection.
39FF7.jpg|Fig. 39.7 Granulomatous rosacea. Discrete red to re
d-brown papules that are a reflection of granulomatous inflammation. Courtesy of
39FF8.jpg|Fig. 39.8 Ocular rosacea. Marked erythema of the co
njunctivae due to inflammation in a patient with mild cutaneous rosacea. Courtes
y of Yale Residents Slide Collection.
39FF9.jpg|Fig. 39.9 Ocular rosacea. Stye on the lower eyelid
margin as a manifestation of ocular rosacea.
39FF10.jpg|Fig. 39.10 Periorificial dermatitis. Multiple fine
papules and pustules in a patient with periocular dermatitis. Courtesy of Ron R
apini, M.D.
39FF11.jpg|Fig. 39.11 Pyoderma faciale. Striking plaque on th
e cheek studded with pustules. Courtesy of Yale Residents Slide Collection.
39FF12.jpg|Fig. 39.12 Steroid rosacea. Involvement of the upp
er cutaneous lip and around the ala nasi is a clue to the diagnosis. (B) Courtes
y of Kalman Watsky, M.D.
39FF13.jpg|Fig. 39.13 Steroid rosacea. More severe disease in
a teenager (A) and young child (B) secondary to application of to
pical corticosteroids. (A) Courtesy of Ron Rapini, M.D.
39FF14.jpg|Fig. 39.14 Lupus miliaris disseminatus faciei. Dis
crete skin-colored to brown papules that, on histologic examination, demonstrate
d granulomas with central caseation necrosis. Courtesy of Yale Residents Slide C
ollection.
39FF15.jpg|Fig. 39.15 Lupus miliaris disseminatus faciei. Pre
dilection of the papules for the periorbital region. Courtesy of Yale Residents
Slide Collection.
39FT1.jpg|Table 39.1 Subtypes and variants of rosacea and their c
haracteristics. Adapted from Wilkin et al. Standard classification of rosace
a: Report of the National Rosacea Society Expert Committee on the Classification
and Staging of Rosacea. J Am Acad Dermatol 2002;46:584–7.
39FT2.jpg|Table 39.2 Primary and secondary features of rosacea. The diagnosis is based on one or more primary features. Adapted from Wilkin e
t al. Standard classification of rosacea: Report of the National Rosacea Society
Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermat
ol. 2002;46:584–7
39FT3.jpg|Table 39.3 Rosacea therapy.
40FF1.jpg|Fig. 40.1 Folliculitis of the beard area due to 
Staphylococcus aureus. Discrete papules are seen posteriorly. Central
ly, there is deeper involvement with plaque formation (sycosis barbae).
40FF2.jpg|Fig. 40.2 Folliculitis due to normal flora. Red-bro
wn perifollicular papules are seen. Some have a collarette of scale. Courtesy of
Ronald Rapini, M.D.

40FF3.jpg|Fig. 40.3 Pseudomonas ‘hot tub’ foll
iculitis. Edematous follicular papules on the flank began to develop 2&#8211
;3 days following the use of a hot tub.
40FF4.jpg|Fig. 40.4 Eosinophilic folliculitis. Multiple pruri
tic follicular papules on the face in a woman with AIDS. There is also postinfla
mmatory hyperpigmentation.
40FF5.jpg|Fig. 40.5 Eosinophilic folliculitis. Multiple folli
cular papules on the chest in the setting of AIDS. There are two punch biopsy si
tes. Note the edematous nature of some of the lesions.
40FF6.jpg|Fig. 40.6 Disseminate and recurrent infundibulofollicul
itis (of Hitch and Lund). Numerous monotonous perifollicular papules on the
chest. Courtesy of Jean Bolognia, M.D.
40FF7.jpg|Fig. 40.7 Lichen spinulosus. Grouped, skin-colored
follicular papules on the extensor surface of the arm. Central keratotic plugs c
an be seen.
40FF8.jpg|Fig. 40.8 Pathogenesis of pseudofolliculitis. Court
esy of MA Abdallah, M.D.
40FF9.jpg|Fig. 40.9 Pseudofolliculitis barbae. Multiple firm
hyperpigmented papules on the lower face and neck (beard distribution).
40FF10.jpg|Fig. 40.10 Acne keloidalis. Keloidal papules and p
laques and scarring alopecia of the posterior scalp. Note the tufts of hair at t
he superior border of the scar (arrows).
40FF11.jpg|Fig. 40.11 Pilonidal sinus and abscess formation at th
e superior portion of the intergluteal cleft. Courtesy of Kalman Watsky, M.D
.
40FF12.jpg|Fig. 40.12 Hidradenitis suppurativa. Biopsy with f
ollicular plugging and connection to dilated apocrine duct. Courtesy of Ronald R
apini, M.D.
40FF13.jpg|Fig. 40.13 Superficial sinus tracts in a patient with
hidradenitis suppurativa. In the absence of active disease they serve as a c
lue to the diagnosis.
40FF14.jpg|Fig. 40.14 Hidradenitis suppurativa. Severe scarri
ng and sinus tract formation of the perianal region, buttocks, and upper thighs.
40FT1.jpg|Table 40.1 Less common forms of superficial folliculiti
s.
40FT2.jpg|Table 40.2 Advice on shaving methods for patients with
pseudofolliculitis barbae.
40FT3.jpg|Table 40.3 Therapeutic approach to pseudofolliculitis b
arbae.
40FT4.jpg|Table 40.4 Advice on using chemical depilatories for ps
eudofolliculitis barbae.
40FT5.jpg|Table 40.5 Therapeutic options for acne keloidalis.
41FF1.jpg|Fig. 41.1 Facial cortical (emotional) hyperhidrosis. Sweat droplets evident on skin above the upper lip, jawline and chin. Reproduc
ed from Hurley HJ. Hyperhidrosis. Curr Opin Dermatol. 1997;4:105–14. Phila
delphia: Rapid Science Publishers.
41FF2.jpg|Fig. 41.2 Hyperhidrosis. Palmar (A) and plan
tar (B) hyperhidrosis. The skin is moist and glistening with eccrine swea
t.
41FF3.jpg|Fig. 41.3 Palmar hyperhidrosis as assessed by the semiquantitative starch paper-iodine technique. Sweating can also be demonstrate
d directly on palmar skin by applying iodine solution, letting it dry and dustin
g on corn starch, as shown in for axillary hyperhidrosis.
41FF4.jpg|Fig. 41.4 ‘Shirt test’. The underarm se
ction of the shirt is stained with sweat. A quantitative measurement can be of t
he size of the stained area produced over a timed period of sweating.
41FF5.jpg|Fig. 41.5 Sweating pattern in axillary hyperhidrosis. Blue-black areas represent the loci of sweating, as demonstrated by the starc
h-iodine technique.
41FF6.jpg|Fig. 41.6 Gustatory sweating in the auriculo-temporal (

Frey) syndrome, a consequence of parotid surgery. The blue-black area repres
enting sweating (starch-iodine technique). Salivary stimulation induced this swe
ating response. Reproduced from Hurley HJ. Hyperhidrosis. Curr Opin Dermatol. 19
97;4:105–14. Philadelphia: Rapid Science Publishers.
41FF7.jpg|Fig. 41.7. Compensatory hyperhidrosis of the face. A Outline of the sites of facial compensatory hyperhidrosis in patients with ext
ensive miliaria. B Facial compensatory hyperhidrosis (upper lip and chin)
in a patient with diabetes mellitus (starch-iodine technique).
41FF8.jpg|Fig. 41.8 Angiokeratoma corporis diffusum (Fabry). A Angiokeratotic lesions of the penis. B Photomicrograph showing lipid in
clusions in kidney tubules. C Eccrine secretory cells are vacuolated and
contain lipid inclusions, which are best seen on electron microscopy (oil red O
stain). Courtesy of James H Graham, M.D.
41FF9.jpg|Fig. 41.9 Miliaria crystallina. Multiple small supe
rficial vesicles with clear fluid.
41FF10.jpg|Fig. 41.10 Miliaria rubra. Multiple erythematous n
onfollicular papules and papulovesicles on the back.
41FF11.jpg|Fig. 41.11 Lafora's disease. Large, purplish-red g
ranules in the outer layer of eccrine duct cells (PAS stain).
41FT1.jpg|Table 41.1 Causes of hyperhidrosis. *Neural mechani
sms participate in these forms of sweating, but it is the vascular or glandular
abnormality that permits the local sweat glands to respond selectively. Reprinte
d with permission from Moschella S, Hurley HV, Dermatology; Philadelphia: WB Sau
nders, 1992.
41FT2.jpg|Table 41.2 Botulinum toxin A (BTX-A) for hyperhidrosis.

41FT3.jpg|Table 41.3 Surgical treatment of axillary hyperhidrosis
.
41FT4.jpg|Table 41.4 Drugs stimulating eccrine sweating directly
or as a side effect.
41FT5.jpg|Table 41.5 Causes of anhidrosis. Reprinted with per
mission from Moschella S, Hurley HV, Dermatology; Philadelphia: WB Saunders, 199
2.
41FT6.jpg|Table 41.6 Systemic disorders that affect the levels of
electrolytes in sweat.
41FT7.jpg|Table 41.7 Types of bromhidrosis. Adapted from Hurl
ey HJ. Apocrine Glands. In Fitzpatrick TB et al (eds) DIGM 4th edit. New York:Mc
Graw-Hill,1993.
41FT8.jpg|Table 41.8 Diagnostic microscopic changes in eccrine gl
ands.
41FT9.jpg|Table 41.9 Heat stress syndromes.
42FF1.jpg|Fig. 42.1 Clinicoserologic correlations of autoimmune c
orrelations of autoimmune connective tissue diseases. Venn diagram represent
ation of major clinicoserologic correlations in the primary AI-CTD that impact t
he skin. Some autoantibodies are specific (boxed) while others are seen in the c
ontext of overlapping clinical features. High levels of U1RNP autoantibody with
overlapping features of all four of these AI-CTD defines the concept of mixed co
nnective tissue disease. With thanks to Jan Dutz, M.D. for contributory comments
.
42FF2.jpg|Fig. 42.2 Detection of antinuclear antibodies on Hep-2
tumor cells. A–D Homogenous pattern; speckled pattern; nucleolar patte
rn; Anti-centromere antibodies. E Anti-double-stranded DNA antibodies bin
ding to the flagellate Crithidia luciliae by indirect immunofluorescence.
42FF3.jpg|Fig. 42.3 Concept of clinical utility in laboratory tes
ting. With permission from ref. 8. With thanks to Jan Dutz, M.D. for contrib
utory comments.
42FF4.jpg|Fig. 42.4 Diagnostic outcome of positive ANA tests.
Outcome of rheumatology evaluations of patients referred for consultations for
positive ANA of undetermined clinical significance. Adapted from data presented
in ref. 10. With thanks to Jan Dutz, M.D. for contributory comments.
42FF5.jpg|Fig. 42.5 Approach to the patient with suspected cutane
ous lupus erythematosus. It should be noted that these recommendations are m
ost relevant within the context of a dermatology practice setting. With thanks t
o Jan Dutz, M.D. for contributory comments.
42FF6.jpg|Fig. 42.6 Approach to the patient with cytoplasmic anti
neutrophil cytoplasmic antibodies (C-ANCA). Courtesy of Julie V Schaffer, M.
D.
42FF7.jpg|Fig. 42.7 Approach to the patient with perinuclear anti
neutrophil cytoplasmic antibodies (P-ANCA). Courtesy of Julie V Schaffer, M.
D.
42FT1.jpg|Table 42.1 Major issues related to the interpretation o
f results of antinuclear antibody assays.
42FT2.jpg|Table 42.2 Autoantibodies associated with lupus erythem
atosus. *Based on most common assay techniques currently employed in clinica
l immunology laboratories. Note that these figures represent the authors’
best estimates based on most recently published data. **Listed in decreasing ord
er of prevalence within categories. Adapted from Sontheimer et al. Adv Dermatol.
1992;7:3–521.
42FT3.jpg|Table 42.3 Autoantibodies encountered in the idiopathic
inflammatory dermatomyopathies (DM/PM). *Using current assay techniques. Ad
apted from Sontheimer et al. Adv Dermatol. 1992;7:3–521.
42FT4.jpg|Table 42.4 Autoantibodies associated with systemic sler
osis (SSc) and localized scleroderma (morphea). A more in-depth discussion o
f these aAb and autoantigens can be found elsewhere15,23,24. RNP, rib
onucleoprotein; HMG, high mobility group *Median prevalence using current assay
techniques. **Higher in patients with linear scleroderma and generalized morphea
. Adapted from Sontheimer et al. Adv Dermatol. 1992;7:3–521.
42FT5.jpg|Table 42.5 Autoantibodies associated with other rheumat
ic diseases having cutaneous manifestations. More in-depth information conce
rning clinicoserological associations can be found elsewhere3,7,8,15,23</su
p>. *Using current assay techniques.** By definition at time of diagnosis.
42FT6.jpg|Table 42.6 Other disorders associated with antineutroph
il cytoplasmic antibodies (ANCA). *C-ANCA are often atypical; in addition, i
mmunofluorescence testing in some laboratories may not distinguish C-ANCA (atypi
cal) from atypical ANCA. **P-ANCA often have antigen specificity other than myel
operoxidase (MPO), e.g. lactoferrin (LF), elastase, cathepsin G (CG), lysozyme,
bactericidal/permeability-increasing protein (BPI), high mobility group non-hist
one chromosomal proteins (HMG1/2), a-enolase, catalase, actin, defensin; C-ANCA
(atypical) have antigen specificity other than proteinase 3, e.g. BPI, lysozyme
or multiple antigens. †Other drugs associated with P-ANCA in single case r
eports include cimetidine, cefotaxime, phenytoin and isotretinoin. ‡Althou
gh primarily associated with C-ANCA, 5–15% of patients with Wegener’
s granulomatosis have P-ANCA; likewise, although primarily associated with P-ANC
A, 5–10% of patients with Churg–Strauss syndrome and ~40% of those w
ith microscopic polyangiitis have C-ANCA; ANCA have also been reported in leukoc
ytoclastic vasculitis of unknown etiology and unclassified vasculitis. C, cytopl
asmic [C-ANCA or C-ANCA (atypical)]; P, perinuclear (P-ANCA); LFTs, liver functi
on tests; ANA, antinuclear antibodies; Ab, antibodies; RF, rheumatoid factor; r/
o, rule out; GBM, glomerular basement membrane; UA, urinalysis; ASO, antistrepto
lysin O. Courtesy of Julie V Schaffer, M.D.
43FF1.jpg|Fig. 43.1 Effect of ultraviolet (UV) radiation on tissu
e response. UV light causes Ro antigen to move to the cell surface, where th
ey bind to anti-Ro antibodies.
43FF2.jpg|Fig. 43.2 Pathogenesis of lupus erythematosus.
43FF3.jpg|Fig. 43.3 Predominant locations of inflammatory infiltr
ates in subsets of cutaneous lupus erythematosus. The types of cutaneous lup
us erythematosus are: acute cutaneous lupus (ACLE), subacute cutaneous lupus (SC
LE), chronic cutaneous lupus (CCLE), tumid lupus (TLE), and lupus panniculitis (
LEP).The primary locations of the infiltrates are as follows: superficial dermis
, ACLE and SCLE; superficial plus deep dermis and periadnexal, DLE; deep dermis,
TLE; and subcutaneous fat, LEP.
43FF4.jpg|Fig. 43.4 Acute cutaneous lupus (ACLE) lesions in a but
terfly distribution on the face of a young woman.
43FF5.jpg|Fig. 43.5 Acute cutaneous lupus (ACLE). The patient
shown in this photo had ACLE lesions on the arms as well as the face.
43FF6.jpg|Fig. 43.6 Subacute cutaneous lupus (SCLE). There ar
e non-scarring, erythematous, slightly scaly plaques on the upper trunk and arms
.
43FF7.jpg|Fig. 43.7 Subacute cutaneous lupus (SCLE) lesions.
Annular plaques with crusted margins. Courtesy of Jean Bolognia, M.D.
43FF8.jpg|Fig. 43.8 Subacute cutaneous lupus (SCLE). The lesi
ons on the hands conform to the typical distribution of lupus lesions, sparing t
he knuckles.
43FF9.jpg|Fig. 43.9 Chronic cutaneous lupus erythematosus (CCLE)
with discoid lesions. The ear is a common site of involvement. Note the cent
ral depigmentation and scarring. In addition to the obvious, intensely inflamed,
indurated lesion on the side of the face, there is a small lesion in the upperm
ost portion of the concha of the ear.
43FF10.jpg|Fig. 43.10 Chronic cutaneous lupus erythematosus (CCLE
) discoid lesion and CCLE vitiligo. The widespread discoid lesions in this p
erson resulted in depigmentation on the face, arms, and trunk.
43FF11.jpg|Fig. 43.11 Tumid lupus. The tumid lupus lesions of
the trunk shown here lack epidermal change and consist of indurated erythematou
s papules.
43FF12.jpg|Fig. 43.12 Lupus panniculitis. The deeply indented
lesions of the arms represent lupus panniculitis. The patient also had lesions
on the face, upper trunk, breasts, and thighs.
43FF13.jpg|Fig. 43.13 Lupus pernio. Violaceous plaques on toe
s, some with scale.
43FF14.jpg|Fig. 43.14 Histology of subacute cutaneous lupus (SCLE
). SCLE displays a superficial and deep perivascular infiltrate of lymphocyt
es with interface changes at the epidermis.
43FF15.jpg|Fig. 43.15 Histology of chronic cutaneous lupus erythe
matosus (CCLE). The inflammatory pattern for CCLE is similar to that of suba
cute cutaneous lupus (SCLE) with prominent periadnexal localization.
43FF16.jpg|Fig. 43.16 Diagnostic algorithm for cutaneous lupus. This algorithm is intended as a guide to diagnosis and should be individualiz
ed for each situation. For example, lesional biopsy for immunofluorescence (IF)
may be performed at the same time as H&E. Less definitive histologic finding
s might sometimes be acceptable if the patient is already known to have systemic
lupus. Whether a diagnosis is clearcut or provisional may be, on occasion, a su
bjective determination. (DIF, direct immunofluorescence.)
43FT1.jpg|Table 43.1 The Ro family.
43FT2.jpg|Table 43.2 Evaluation for systemic lupus erythematosus.
 ANA, anti-nuclear antibodies; BUN, blood urea nitrogen; CBC, complete blood
count; ESR, erythrocyte sedimentation rate, Sm, Smith
43FT3.jpg|Table 43.3 The American College of Rheumatology 1982 re
vised criteria for classification of systemic lupus erythematosus80.
43FT4.jpg|Table 43.4 Therapeutic ladder for lupus erythematosus
44FF1.jpg|Fig. 44.1 Violaceous poikiloderma of the face.
44FF2.jpg|Fig. 44.2 Violaceous poikiloderma of the face, plus thi
n plaques on the elbows that are sometimes misdiagnosed as psoriasis.
44FF3.jpg|Fig. 44.3 Violaceous poikiloderma of the hands with sec
ondary lichenoid changes.
44FF4.jpg|Fig. 44.4 Gottron's sign with violaceous poikiloderma o
ver the knuckles.
44FF5.jpg|Fig. 44.5 Gottron's papules, with the knuckle lesions s
howing a papular quality caused by rubbing.

44FF6.jpg|Fig. 44.6 Cuticular dystrophy and nailfold telangiectas
ias in a patient with dermatomyositis. Note the flat-topped (lichenoid) papu
les over the distal interphalangeal joints. The nailfold telangiectasias of scle
roderma are similar in appearance.
44FF7.jpg|Fig. 44.7 Calcinosis cutis on the abdomen of a child wi
th dermatomyositis.
44FF8.jpg|Fig. 44.8 Interface dermatitis in biopsy of dermatomyos
itis. (courtesy of Omar Sangueza MD)
44FF9.jpg|Fig. 44.9 Higher power view of vacuolar alteration of b
asal layer. (courtesy of Omar Sangueza MD)
44FF10.jpg|Fig. 44.10 Patient evaluation for adults with dermatom
yositis. Evaluation for children is similar but without the malignancy evalu
ation, although pediatricians are sometimes reluctant to endorse electromyograms
or muscle biopsy.
44FF11.jpg|Fig. 44.11 T2-weighted MR image of the pelvic region i
n a normal control patient.
44FF12.jpg|Fig. 44.12 T2-weighted MR image of the pelvic region i
n a patient with dermatomyositis. This shows increased signal intensity (whi
te color) diffusely in multiple muscle groups. The increased signal correlates w
ith inflammation.
44FF13.jpg|Fig. 44.13 T3-weighted MRI images of the proximal thig
h in a patient with dermatomyositis. Note the increased signal density, prim
arily in the extensor muscles. The increased signal correlates with inflammation
.
44FF14.jpg|Fig. 44.14 Cross-sectional ultrasound image from norma
l (control) triceps muscle.
44FF15.jpg|Fig. 44.15 Ultrasound image from affected triceps musc
le, showing increase in interstitial echoes.
44FT1.jpg|Table 44.1 Clinical features of 54 patients in a dermat
ology-based series.
44FT2.jpg|Table 44.2 Pathogenesis of dermatomyositis. HLA, hu
man leukocyte antigen; ICAM, intracellular adhesion molecule; UVB, ultraviolet B
44FT3.jpg|Table 44.3 Serum autoantibodies in polymyositis and der
matomyositis patient subsets. With permission from Klippel and Dieppe23
.
44FT4.jpg|Table 44.4 Antiaminoacyl-tRNA synthetase antibodies and
their associated antigens in polymyositis/dermatomyositis. With permission
from Klippel and Dieppe23.
44FT5.jpg|Table 44.5 Differential diagnosis of dermatomyositis.
44FT6.jpg|Table 44.6 Therapeutic ladder for dermatomyositis.
Key to evidence-based support: double-blind studies; clinical series; anecdotal
evidence. UVA, ultraviolet A.
45FF1.jpg|Fig. 45.1 Interactions between endothelial cells, leuko
cytes and fibroblasts in scleroderma pathogenesis. ECM, extracellular matrix
; EC, endothelial cell; TGF, transforming growth factor; PDGF, platelet-derived
growth factor; IGF, insulin-like growth factor.
45FF2.jpg|Fig. 45.2 Scleroderma. Leukoderma with retention of
perifollicular pigmentation.
45FF3.jpg|Fig. 45.3 Facial features in a patient with systemic sc
lerosis (scleroderma). Close-up of mat telangiectasias.
45FF4.jpg|Fig. 45.4 Calcinosis cutis of the thumb in a patient wi
th scleroderma.
45FF5.jpg|Fig. 45.5 Scleroderma. Pitted scar of the digital p
ulp in a patient with scleroderma.
45FF6.jpg|Fig. 45.6 Scleroderma. There is a dense sclerosis o
f the dermis with decreased adnexal structures, and ‘trapping’ of re
maining adnexal structures encased by collagen. Sparse perivascular lymphocytes
are present. Courtesy of Ron Rapini, M.D.
45FT1.jpg|Table 45.1 Major clinical and laboratory manifestations

of systemic sclerosis and other selected conditions characterized by fibrosis. EMS, eosinophilia myalgia syndrome; ++, almost always; +, common; ±, so
metimes; –, rare or unusual.
45FT2.jpg|Table 45.2 Clinical and laboratory features in the diff
erential diagnosis of Raynaud’s phenomenon. From Klippel et al. (eds).
Rheumatology 2nd edit. St Louis: Mosby. © Elsevier 1998.
45FT3.jpg|Table 45.3 Comparison of clinical and laboratory featur
es of diffuse and limited scleroderma. From Klippel et al. (eds). Rheumatolo
gy 2nd edit. St Louis: Mosby. © Elsevier 1998.
45FT4.jpg|Table 45.4 Evaluation of internal organ involvement in
patients with scleroderma. *Especially if recent-onset systemic sclerosis.
45FT5.jpg|Table 45.5 Sclerodermoid differential diagnosis.
45FT6.jpg|Table 45.6 Differential diagnosis of Raynaud’s ph
enomenon. From Klippel et al. (eds). Rheumatology 2nd edit. St Louis: Mosby.
© Elsevier 1998.
46FF1.jpg|Fig. 46.1 Juvenile rheumatoid arthritis. Evanescent
pink papules and plaques in a child.
46FF2.jpg|Fig. 46.2 Relapsing polychondritis. Erythema and sw
elling of the ear with sparing of the earlobe. Courtesy of Kalman Watsky MD.
46FF3.jpg|Fig. 46.3 Pigmented purpura-like lesions in a patient w
ith Sjögren's syndrome.
46FF4.jpg|Fig. 46.4 Cutaneous vasculitis (palpable purpura) and n
on-palpable purpura of the lower extremities in a patient with Sjögren's sy
ndrome and cryoglobulinemia type II who developed glandular marginal B-cell lymp
homa.
46FF5.jpg|Fig. 46.5 Rheumatoid arthritis. Nodules over the sm
all joints of the hands. Courtesy of Kalman Watsky MD.
46FF6.jpg|Fig. 46.6 Rheumatoid vasculitis. Involvement of med
ium-sized vessels in a patient with high-titer rheumatoid factor who presented w
ith livedo reticularis and intractable ulcers of the lower extremities.
46FF7.jpg|Fig. 46.7 Evaluation of a patient with suspected rheuma
toid vasculitis (involving medium-sized vessels) in whom cutaneous histologic fi
ndings are negative or inconclusive.
46FF8.jpg|Fig. 46.8 Patient with rheumatoid arthritis who develop
ed chronic relapsing pyoderma gangrenosum of the lower extremities.
46FF9.jpg|Fig. 46.9 Rheumatoid papules on the elbows in a patient
with rheumatoid arthritis with high-titer rheumatoid factor.
46FF10.jpg|Fig. 46.10 Evaluation of a patient with palisaded necr
otizing granulomas and suspected rheumatologic disorder.
46FT1.jpg|Table 46.1 Differential diagnosis of periodic fevers wi
th arthritis and an exanthem.
46FT2.jpg|Table 46.2 Dermatologic conditions reported in patients
with rheumatoid arthritis.
46FT3.jpg|Table 46.3 Histologic evidence of rheumatoid vasculitis
involving mediumsized vessels, depending upon type of cutaneous lesion.
46FT4.jpg|Table 46.4 Specific ulcerative diseases associated with
rheumatoid arthritis.
47FF1.jpg|Fig. 47.1 Approach to the patient with suspected primar
y dermal mucinosis. Courtesy of Yale Residents Slide Collection.
47FF2.jpg|Fig. 47.2 Scleromyxedema. Hundreds of small papules
and induration of the forehead in a patient with paraproteinemia. This patient'
s skin and paraproteinemia responded to a stem cell transplant. Courtesy of Ron
Rapini, MD.
47FF3.jpg|Fig. 47.3 Scleromyxedema. Typical deep longitudinal
furrows of the glabella.
47FF4.jpg|Fig. 47.4 Localized lichen myxedematosus of the discret
e type. Persistent whitish papules on the arms.
47FF5.jpg|Fig. 47.5 Acral persistent papular mucinosis. Skincolored papules on the dorsal aspect of the hands.
47FF6.jpg|Fig. 47.6 Histopathology of scleromyxedema. Typical

triad of fibrosis, proliferation of irregularly arranged fibroblasts and inters
titial deposits of mucin in the upper and mid-reticular dermis.
47FF7.jpg|Fig. 47.7 Histopathology of lichen myxedematosus (discr
ete type). Mucin deposits splay collagen bundles in the dermis, but there is
only slight fibroblast proliferation and no sclerosis.
47FF8.jpg|Fig. 47.8 Lichen myxedematosus of the discrete type dem
onstrating mucin accumulation in the dermis. Alcian blue stain (pH 2.5).
47FF9.jpg|Fig. 47.9 Reticular erythematous mucinosis. Erythem
atous papules coalesce into a reticulated pattern or plaque-like lesions in the
middle of the chest. Courtesy of Yale Residents Slide Collection.
47FF10.jpg|Fig. 47.10 Scleredema. Diffuse induration of the u
pper part of the body with slight erythema. Note that the site of a previous bio
psy can be seen. Courtesy of Yale Residents Slide Collection.
47FF11.jpg|Fig. 47.11 Pretibial myxedema. Purple-brown plaque
on the shin of a patient with Graves' disease.
47FF12.jpg|Fig. 47.12 Generalized myxedema in adult hypothyroidis
m. The face is puffy with a dull expression and the hair is dry.
47FF13.jpg|Fig. 47.13 Lupus cutaneous mucinosis. Skin-colored
, sometimes reddish, papules and nodules leading to a ‘lumpy’ appear
ance of the chest.
47FF14.jpg|Fig. 47.14 Pinkus' follicular mucinosis. Follicula
r papules merging into a scaly plaque with alopecia.
47FT1.jpg|Table 47.1 Staining characteristics of acid glycosamino
glycans (mucopolysaccharides)
47FT2.jpg|Table 47.2 Primary (distinctive) cutaneous mucinoses
47FT3.jpg|Table 47.3 Disorders associated with histologic deposit
ion of mucin (secondary mucinoses)
47FT4.jpg|Table 47.4 Clinicopathologic subsets of lichen myxedema
tosus (papular mucinosis)
47FT5.jpg|Table 47.5 Diagnostic criteria of lichen myxedematosus
(papular mucinosis)
47FT6.jpg|Table 47.6 Clinical and microscopic criteria for distin
guishing (angio)myxoma from focal cutaneous mucinosis
47FT7.jpg|Table 47.7 Histologic criteria for distinguishing Pinku
s’ follicular mucinosis from follicular mucinosis with lymphoma.
48FF1.jpg|Fig. 48.1 Nodular amyloidosis. There are diffuse eo
sinophilic deposits with characteristic fissuring. Courtesy of Ron Rapini, MD.
48FF2.jpg|Fig. 48.2 Staining for amyloid. Congo red staining
of amyloid deposits in the papillary dermis on light microscopy (left). There is
characteristic green birefringence with polarized light (right). Courtesy of th
e St John's Institute of Dermatology.
48FF3.jpg|Fig. 48.3 Electron microscopy of cutaneous amyloid depo
sits. There are clusters of filamentous deposits and 7–10 nm nonbranching fibrils. Courtesy of the St John's Institute of Dermatology.
48FF4.jpg|Fig. 48.4 Characteristic cross-β-pleated sheet arr
angement of amyloid fibrils. Schematic representation. Adapted from Glenner
.
48FF5.jpg|Fig. 48.5 Hyperpigmentation of macular and biphasic amy
loidosis with the characteristic rippled pattern.
48FF6.jpg|Fig. 48.6 Lichen amyloidosis. Keratotic, hyperpigme
nted plaques on the legs. Inset, closer view of individual keratotic papules. Co
urtesy of the St John's Institute of Dermatology.
48FF7.jpg|Fig. 48.7 Nodular amyloidosis. A Lesions on the pla
ntar surface. B,C Photomicrographs demonstrating extensive amyloid deposi
tion within blood vessel walls extending into the deep dermis.
48FF8.jpg|Fig. 48.8 Multiple papules of amyloidosis in a patient
with systemic scleroderma.
48FF9.jpg|Fig. 48.9 AL (primary systemic) amyloidosis. Macrog
lossia with dental impression on the tongue.

48FF10.jpg|Fig. 48.10 AL amyloidosis. Periorbital ecchymoses
– ‘raccoon sign’. Courtesy of the St John's Institute of Derma
tology.
48FF11.jpg|Fig. 48.11 Primary systemic amyloidosis. There are
numerous waxy and translucent facial papules.
48FF12.jpg|Fig. 48.12 Evaluation of a patient with suspected prim
ary systemic amyloidosis.
48FT1.jpg|Table 48.1 Clinical classification of amyloidosis.
48FT2.jpg|Table 48.2 Chemical classification of amyloidoses (
modified from Westermark et al.9).
48FT3.jpg|Table 48.3 Histologic criteria used to define amyloid<s
up>2.
48FT4.jpg|Table 48.4 Treatment of macular and lichenoid amyloidos
is. Key to evidence-based support: double-blind studies; clinical series; an
ecdotal evidence.
49FF1.jpg|Fig. 49.1 Tophaceous gout. The deposits create a mu
ltilobulated appearance.
49FF2.jpg|Fig. 49.2 Tophaceous gout. The erythema reflects su
rrounding inflammation.
49FF3.jpg|Fig. 49.3 Histologic features of gout. A Deposits o
f amorphous, acellular material within the dermis. B Higher magnification
. Needle-like spaces are present within the amorphous deposits and histiocytes,
and multinucleated giant cells surround the deposits.
49FF4.jpg|Fig. 49.4 Lipoid proteinosis. Beaded eyelid papules
. Courtesy of Ron Rapini, M.D.
49FF5.jpg|Fig. 49.5 Lipoid proteinosis. Verrucous plaque on t
he elbow. Courtesy of Ron Rapini, M.D.
49FF6.jpg|Fig. 49.6 Lipoid proteinosis. Hyperkeratosis and ve
rtically oriented eosinophilic deposits. Courtesy of Ron Rapini, M.D.
49FF7.jpg|Fig. 49.7 Type VI mucopolysaccharidosis. A 3-year-o
ld with coarse features and stunted growth.
49FT1.jpg|Table 49.1 Disorders with dermal deposits – histo
logic features. EPP, erythropoietic protoporphyria; BMZ, basement membrane z
one.
49FT2.jpg|Table 49.2 Classification of hyperuricemia. Adapted
from Sutej et al.6.
49FT3.jpg|Table 49.3 The mucopolysaccharidoses (MPS). AR, aut
osomal recessive. Adapted with permission from McGovern MM. Lysosomal storage di
seases. In: Braunwald E, Fauci AS, Kasper D, Hauser S, Longo D, Jameson J. Harri
son’s Principles of Internal Medicine. 15th edn. New York: McGraw Hill; 20
01.
50FF1.jpg|Fig. 50.1 The heme biosynthetic pathway.
50FF2.jpg|Fig. 50.2 An approach to the patient with blistering on
the skin.
50FF3.jpg|Fig. 50.3 An approach to the patient with phototoxic bu
rning.
50FF4.jpg|Fig. 50.4 Porphyria cutanea tarda in a patient with hep
atitis C virus infection. Multiple erosions with hemorrhagic crusts are seen
as well as an intact blister on the lateral fourth finger. Courtesy of Ron Rapi
ni, M.D.
50FF5.jpg|Fig. 50.5 Porphyria cutanea tarda. Erosions and sca
rs on the forehead ans scalp of a man with chronic renal failure receiving perit
oneal dialysis. Courtesy of Ron Rapini, M.D.
50FF6.jpg|Fig. 50.6 Porphyria cutanea tarda. Marked fragility
with multiple hemorrhagic crusts, erosions and milia, as well as scars.
50FF7.jpg|Fig. 50.7 Hepatoerythropoietic porphyria. Hypertric
hosis and severe scarring with ectropion are seen, resulting in a clinical appea
rance similar to congenital erythropoietic porphyria. Courtesy of Jose Mascaro,
M.D.
50FF8.jpg|Fig. 50.8 Histologic features of porphyria cutanea tard

a. A Subepidermal blister with minimal ‘cell-poor’ dermal inflam
matory infiltrate (H&E). B Festooning of dermal papillae with PAS-pos
itive deposits within the walls of blood vessels (PAS stain). Courtesy of Ron Ra
pini, M.D.
50FF9.jpg|Fig. 50.9 Dialysis-associated pseudoporphyria. Vesi
cles formed on the dorsal aspects of the hands in this patient with chronic rena
l failure. Courtesy of Kalman Watsky, M.D.
50FF10.jpg|Fig. 50.10 Erythropoietic protoporphyria. Erythema
and hemorrhagic crusts on the nose as well as fingers in a young girl.
50FF11.jpg|Fig. 50.11 Erythropoietic protoporphyria. Subtle s
carring on the nose, not the linear scars on the upper lip of this 6-year-old ch
ild.
50FF12.jpg|Fig. 50.12 Histologic features of erythropoietic proto
porphyria. A Eosinophilic deposits around blood vessels are more pronounced
than in PCT. B Dermal deposits are highlighted by this PAS stain.
50FF13.jpg|Fig. 50.13 Congenital erythropoietic porphyria. Mi
ld erythrodontia (A) and severe mutilation of the hands (B). Court
esy of Jose Mascaro, M.D.
50FF14.jpg|Fig. 50.14 Fluorescence of circulating red blood cells
. When exposed to UVA light, fluorescence is seen in congenital erythropoiet
ic porphyria (A) as opposed to transient fluorescence in erythropoietic p
rotoporphyria (B) which is more difficult to photograph. Courtesy of Jose
Mascaro, M.D.
50FT1.jpg|Table 50.1 Classification of the porphyrias. *Eryth
ropoietic porphyrias, the remainder are hepatic.
50FT2.jpg|Table 50.2 Investigative tests used in the diagnosis of
porphyria.
50FT3.jpg|Table 50.3 Porphyria cutanea tarda: clinical features,
disease associations and baseline investigations.
50FT4.jpg|Table 50.4 Therapeutic approaches to the porphyrias.
50FT5.jpg|Table 50.5 Erythropoietic protoporphyria: clinical feat
ures, complications, and baseline investigations.
51FF1.jpg|Fig. 51.1 Dystrophic calcification in a patient with CR
EST syndrome.
51FF2.jpg|Fig. 51.2 Mechanisms of hyperphosphatemia and metastati
c calcification in patients with chronic renal failure.
51FF3.jpg|Fig. 51.3 Calciphylaxis in a patient with chronic renal
failure. A Typical reticulated, violaceous plaques that usually precede ulc
eration. B Although the eruption may be clinically impressive, the degree
of calcification seen histologically may be subtle; perivascular deposition of
calcium is seen.
51FF4.jpg|Fig. 51.4 Histology of osteoma cutis. Islands of bo
ne formation within the dermis. Osteoblasts and bone marrow elements can also oc
casionally be seen in lesions of osteoma cutis.
51FF5.jpg|Fig. 51.5 Progressive osseous heteroplasia in a child.
A Small whitish papules can be seen on the ankle of this 1 year-old girl. B Histologic features consist of deposits of calcium more superficially, of
ten with foci of cartilage and bone formation in the subcutaneous tissue.
51FF6.jpg|Fig. 51.6 Algorithm for the evaluation of a patient wit
h cutaneous or subcutaneous ossification.
51FF7.jpg|Fig. 51.7 Miliary osteoma cutis. A Multiple discret
e whitish papules developed on the face of a patient with no previous history of
acne. B The foci of ossification are readily apparent on CT scan.
51FT1.jpg|Table 51.1 Disorders of cutaneous calcification
51FT2.jpg|Table 51.2 Laboratory evaluation of patients with cutan
eous calcification/ossification
52FF1.jpg|Fig. 52.1 Malnutrition. Classification and causes.
52FF2.jpg|Fig. 52.2 Marasmus. This child is emaciated and the
re is both hyperpigmentation and desquamation of the skin.

52FF3.jpg|Fig. 52.3 Marasmus. Multiple purpuric lesions are s
een.
52FF4.jpg|Fig. 52.4 Kwashiorkor. This child's buttocks and le
gs show tense edema, scaling and areas of erythema with desquamation.
52FF5.jpg|Fig. 52.5 Kwashiorkor. This child's arm has edema,
superficial epidermal necrosis with an ‘enamel paint’ appearance.
52FF6.jpg|Fig. 52.6 Vitamin A deficiency. Blindness due to vi
tamin A deficiency. Courtesy of Peter Ehrnstrom, M.D.
52FF7.jpg|Fig. 52.7 Scurvy. A Corkscrew hairs and perifollicu
lar hemorrhage on the lower extremities. B Hemorrhage beneath the buccal
mucosa.
52FF8.jpg|Fig. 52.8 Pellagra. A Hyperpigmention with desquama
tion. B Hyperpigmented desquamation of the distal lower extremity. Note t
he shiny shellac-like appearance on the lateral ankle.
52FF9.jpg|Fig. 52.9 Zinc deficiences. Genetic (A, B) a
nd acquired (C, D) forms. Both have erythema with erosions (A, C)
as well as crusting and desquamation.
52FF10.jpg|Fig. 52.10 Menkes' syndrome. This child has the ch
aracteristic pale skin and sparse kinky hair.
52FT1.jpg|Table 52.1 Characteristics of protein–energy maln
utrition and essential fatty acid deficiency.
52FT2.jpg|Table 52.2 Frequent dermatoses in obese individuals
53FF1.jpg|Fig. 53.1 Rheumatoid papules. Multiple red-brown pa
pules, some with scale crust, on the lower extremities.
53FF2.jpg|Fig. 53.2 Pseudoporphyria in a patient with rheumatoid
arthritis. The cause was a non-steroidal anti-inflammatory drug. Courtesy of
Kalman Watsky, M.D.
53FF3.jpg|Fig. 53.3 Acanthosis nigricans and the sign of Leser-Tr
élat. This patient had a gastric carcinoma. Courtesy of Neil A Fenske M
.D.
53FF4.jpg|Fig. 53.4 Bazex syndrome (acrokeratosis paraneoplastica
) in a patient with esophageal carcinoma. Note the involvement of the distal
nose.
53FF5.jpg|Fig. 53.5 Erythema gyratum repens. This patient had
cancer of the breast.
53FF6.jpg|Fig. 53.6 Hypertrichosis lanuginosa. This patient h
ad a pancreatic cancer. Courtesy of Joseph J Chanda M.D.
53FF7.jpg|Fig. 53.7 Acute febrile neutrophilic dermatosis (Sweet'
s syndrome) associated with acute myelogenous leukemia. The hemorrhagic comp
onent is secondary to severe thrombocytopenia.
53FF8.jpg|Fig. 53.8 Paget's disease of the breast. A chronic,
erythematous, scaly plaque surrounds the nipple.
53FF9.jpg|Fig. 53.9 Paraneoplastic pemphigus. This patient ha
d no history of malignancy, nor was one discovered with careful assessment, yet
he had clinical features and immunopathologic confirmation for this immunobullou
s disorder.
53FF10.jpg|Fig. 53.10 Multicentric reticulohistiocytosis. Mul
tiple papulonodules are present on the dorsal aspect of the hands in this adoles
cent. There was no evidence of a malignancy.
53FF11.jpg|Fig. 53.11 Acanthosis nigricans of the neck in a patie
nt with insulin resistance and obesity. Note the velvety texture of the skin
.
53FF12.jpg|Fig. 53.12 Necrotizing migratory erythema-like lesion
in a patient with both hepatitis C virus and HIV infections.
53FF13.jpg|Fig. 53.13 Diabetic dermopathy. Note the brown mac
ules and patches in the shins.
53FF14.jpg|Fig. 53.14 Bullous diabeticorum. Non-inflammatory
bullae on the lower extremity in a patient with diabetes mellitus.
53FF15.jpg|Fig. 53.15 Necrobiosis lipoidica. Controversy exis
ts about the exact risk of diabetes mellitus in such patients, but it is much mo
re strongly associated with diabetes than is granuloma annulare.
53FF16.jpg|Fig. 53.16 Acanthosis nigricans over the knuckles in a
patient with insulin resistance and obesity. Acanthosis nigricans can invol
ve extensor surfaces as well as flexure areas. Courtesy of Jean Bolognia M.D.
53FF17.jpg|Fig. 53.17 Neurotropic ulcers on the toes of a patient
with diabetic sensory neuropathy.
53FF18.jpg|Fig. 53.18 Eruptive xanthomas are frequently associate
d with poorly controlled diabetes mellitus. This patient was first discovere
d to have diabetes following the appearance of these yellow-red papules.
53FF19.jpg|Fig. 53.19 Hemochromatosis. There is diffuse hyper
pigmentation (bronzing) of the skin.
53FF20.jpg|Fig. 53.20 ‘Buffalo hump’ of Cushing's dis
ease due to fat redistribution.
53FF21.jpg|Fig. 53.21 Cushing's disease with multiple striae.
This patient had a pituitary adenoma.
53FF22.jpg|Fig. 53.22 Pyoderma gangrenosum. Patients with inf
lammatory bowel disease usually have typical lesions such as this.
53FF23.jpg|Fig. 53.23 Peristomal pyoderma gangrenosum. This p
atient had a total colectomy for ulcerative colitis many years prior to the onse
t of this lesion.
53FF24.jpg|Fig. 53.24 ‘Metastatic’ Crohn's disease. Non-contiguous granulomatous inflammation of the skin is often manifested by
deep inflammatory fissures in the inguinal folds.
53FF25.jpg|Fig. 53.25 Hereditary hemorrhagic telangiectasia.
Multiple small bright red macules and papules on the tongue and lips.
53FF26.jpg|Fig. 53.26 Blue rubber bleb nevus syndrome. Severa
l venous malformations are evident on this patient's tongue.
53FF27.jpg|Fig. 53.27 Porphyria cutanea tarda presenting with yel
low-brown morpheaform plaques. The plaques were in sun-exposed areas in this
patient with a history of alcohol abuse.
53FF28.jpg|Fig. 53.28 Antiphospholipid antibody syndrome. In
addition to bland thromboses, these patients may have cardiac valvular vegetatio
ns.
53FF29.jpg|Fig. 53.29 Relapsing polychondritis. The inflammat
ion spares the earlobes which lack cartilage.
53FF30.jpg|Fig. 53.30 Periorificial and facial papules of sarcoid
osis. The presence of lesions on the nasal rim is often associated with gran
ulomatous inflammation of the upper respiratory tract.
53FF31.jpg|Fig. 53.31 Calciphylaxis. This patient presented w
ith these necrotic skin lesions and was found to have severe end-stage renal dis
ease due to amyloidosis of the kidney.
53FT1.jpg|Table 53.1 Cutaneous conditions that are reported in as
sociation with rheumatoid arthritis.
53FT2.jpg|Table 53.2 Criteria used to associate a dermatosis and
malignancy (Curth’s postulates).
53FT3.jpg|Table 53.3 Paraneoplastic dermatoses.
53FT4.jpg|Table 53.4 Selected dermatologic associations of diabet
es mellitus. Adapted from: Jorizzo JL, Callen JP. Dermatologic manifestation
s of internal disease. In:Arndt KA, Robinson JK, LeBoit PE, et al. (eds). Cutane
ous Medicine and Surgery. Philadelphia: WB Saunders. 1996:1863–89.
53FT5.jpg|Table 53.5 Dermatologic manifestations of hyperthyroidi
sm.
53FT6.jpg|Table 53.6 Dermatologic manifestations of hypothyroidis
m.
53FT7.jpg|Table 53.7 Dermatologic manifestations of Cushing&#8217
;s disease (syndrome). *This same change is indicative of insulin resistance
and occurs in HIVassociated lipodystrophy.
53FT8.jpg|Table 53.8 Selected dermatologic manifestations of Addi
son’s disease. MSH, melanocyte-stimulating hormone.
53FT9.jpg|Table 53.9 Associated cutaneous findings in Crohn&#8217

;s disease and ulcerative colitis.
53FT10.jpg|Table 53.10 Cutaneous diseases associated with gastroi
ntestinal hemorrhage. Adapted from: Callen JP, Fabre VC. Cutaneous manifesta
tions of systemic disease. In: Moschella SL, Hurley HJ (eds). Dermatology. Phila
delphia: WB Saunders. 1992:1682–718 and Jorizzo JL, Callen JP. Dermatologi
c manifestations of internal disease. In: Arndt KA, Robinson JK, LeBoit PE , et
al. (eds). Cutaneous Medicine and Surgery. Philadelphia: WB Saunders. 1996:1863&
#8211;89.
53FT11.jpg|Table 53.11 Dermatologic aspects of liver disease.
53FT12.jpg|Table 53.12 Cardiocutaneous abnormalities in multisyst
em disorders. Adapted from: Jorizzo JL, Callen JP. Dermatologic manifestatio
ns of internal disease. In: Arndt KA, Robinson JK, LeBoit PE et al. (eds). Cutan
eous Medicine and Surgery. Philadelphia: WB Saunders. 1996:1863–89. CNS, c
entral nervous system; EKG, electrocardiogram; CVA, cerebrovascular accident; LE
, lupus erythematosus; NAME, nevi, atrial myxoma, myxoma of the skin, ephelides;
LAMB, lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi; GI, gastroint
estinal.
53FT13.jpg|Table 53.13 Pulmonary disease and the skin. A&#821
1;V, arteriovenous.
53FT14.jpg|Table 53.14 Renal disease and the skin. ESRD, end
stage renal disease; LE, lupus erythematosus; GI, gastrointestinal; CNS, central
nervous system; CVA, cerebrovascular accident; PTH, parathyroid hormone; CREST,
calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly & telang
iectasias.
54FF1.jpg|Fig. 54.1 The polymorphic locus. Locus A represents
a polymorphic locus with three different alleles. The example shows a family in
which the father is homozygous for allele 1 and the mother is heterozygous for
alleles 2 and 3. The son of this family has inherited allele 1 from the father a
nd allele 3 from the mother, and is thus heterozygous (1,3).
54FF2.jpg|Fig. 54.2 Mendelian patterns of inheritance. A Auto
somal dominant epidermolysis bullosa simplex superficialis (modified from ref. 2
9); B Autosomal recessive woolly hair, palmoplantar keratoderma and heart
disease (modified from ref. 30); C X-linked recessive immune deficiency
and hypohidrotic ectodermal dysplasia (modified from ref. 31); D X-linked
dominant incontinentia pigmenti (modified from ref. 32); E Y-linked reti
nitis pigmentosa (modified from ref. 33).
54FF3.jpg|Fig. 54.3 Variations to the basic Mendelian patterns of
inheritance. A Reduced penetrance in a pedigree with autosomal dominant ret
initis pigmentosa (modified from ref. 38); B High degree of consanguinity
in a family with hypotrichosis, with affected family members in several generat
ions; C Pseudodominant inheritance in autosomal recessive atrichia with p
apular lesions (APL). The inheritance of APL in this pedigree mimics an autosoma
l dominant pattern of inheritance resulting from the mating between a patient ho
mozygous for the causative genetic mutation (II:2) and an unaffected carrier (mo
dified from ref. 39). The symbols commonly used for pedigree drawing are indicat
ed at the bottom of Figure 54.2.
54FF4.jpg|Fig. 54.4 Genomic imprinting. Genes A and B are imp
rinted in males and females, respectively. Somatic cells in males and females wi
ll maintain the imprinting pattern present in the gametes. In the germ line, on
the contrary, the imprinting will be erased and the corresponding sex-specific i
mprint established.
54FF5.jpg|Fig. 54.5 Haplotypes for a chromosomal region containin
g four polymorphic loci, A, B, C and D. Loci very close together will rarely
be separated by recombination.
54FF6.jpg|Fig. 54.6 Types of polymorphisms. SNPs (A
, B) consist of single base substitutions. A Point substitution (unde
rlined) replacing a cytosine, C, with a thymidine, T, identified by DNA sequenci
ng. B The sequence ggatcc is the target site for the restriction e
nzyme BamHI. In the presence of this particular sequence, the enzyme will
cut the DNA into two fragments, detected as two bands in an agarose gel (allele
2). If this sequence is altered by a base substitution and, therefore, not reco
gnized by the enzyme, no cleavage occurs (allele 1). A polymorphism that affects
the recognition site for a restriction enzyme is referred to as an RFLP (restri
ction fragment length polymorphism). C Example of microsatellites. The re
peat unit of the microsatellites shown here is the dinucleotide (CA). The number
of tandem repeats of the (CA) unit can vary in each allele. The figure shows tw
o individuals heterozygous for the number of repeats of this dinucleotide. The d
ifferences in length between these three alleles appear as bands of DNA of diffe
rent sizes in a polyacrylamide gel.
54FF7.jpg|Fig. 54.7 Two-point LOD score values for markers on chr
omosome 1. Values greater than 3 (in red) indicate linkage between the pheno
type and the marker. The negative values for markers D1S209 and D1S2798 at a rec
ombination fraction of 0 indicate that genetic recombination has been observed b
etween the phenotype and the marker.
54FF8.jpg|Fig. 54.8 Haplotype analysis for the refinement of a li
nkage interval. The disease-associated haplotype, 4 4 1 1 3 2 (shaded in blu
e) has been broken by genetic recombination in three family members (stars). The
two key recombinant individuals, III:8 and IV:1, have allowed the narrowing of
the disease interval. The symbols commonly used for pedigree drawing are indicat
ed at the bottom of Figure 54.2.
54FF9.jpg|Fig. 54.9 Pedigrees with alopecia areata as an example
of multifactorial dermatologic disease. Although some of the pedigrees indiv
idually can mimic Mendelian pattern of inheritance (A and B), othe
rs show a more complex pattern (C), in which the disease is inherited thr
ough two unrelated branches of the family. A single mode of inheritance cannot b
e established for the disease as a group. The symbols commonly used for pedigree
drawing are indicated at the bottom of Figure 54.2.
54FT1.jpg|Table 54.1 Examples of allelic heterogeneity in genoder
matoses. GJB3, gene encoding connexin 31; AD, autosomal dominant; AR,
autosomal recessive; EBS, epidermolysis bullosa simplex.
54FT2.jpg|Table 54.2 Examples of genodermatoses with genetic or l
ocus heterogeneity. AP3B1, gene for beta-3A subunit of AB3; KRT5, keratin 5 gene; KRT14, keratin 14 gene; HPS1, HPS3 and HPS4
, genetic loci or genes for Hermansky–Pudlak syndrome.
55FF1.jpg|Fig. 55.1 Carvajal syndrome (striate keratoderma with w
oolly hair and cardiomyopathy). This syndrome differs from Naxos disease bot
h clinically (striate versus diffuse keratoderma) and at the molecular level (de
smoplakin versus plakoglobin disorder). Courtesy of Luis Carvajal, M.D.
55FF2.jpg|Fig. 55.2 Conradi–Hünermann–Happle syn
drome. This syndrome is characterized by congenital ichthyosiform erythroder
ma with systematized follicular hyperkeratoses along Blaschko's lines.
55FF3.jpg|Fig. 55.3 CHILD syndrome. In congenital hemidysplas
ia with ichthyosiform nevus and limb defects (CHILD syndrome), the inflammatory
nevus is characterized by a unique lateralization pattern and does not show any
relationship to hair follicles.
55FF4.jpg|Fig. 55.4 CHILD syndrome. On occasion, CHILD syndro
me may show a bilateral, almost symmetrical involvement.
55FF5.jpg|Fig. 55.5 MIDAS syndrome. Microphthalmia, dermal ap
lasia and sclerocornea are caused by a deletion at Xp22 and may be associated wi
th Aicardi syndrome (agenesis of the corpus callosum with a chorioretinal abnorm
ality) in the form of a contiguous gene syndrome. Courtesy of J Mücke, M.D.
55FF6.jpg|Fig. 55.6 Ichthyosiform hyperkeratosis. This clinic
al feature is characteristic of trisomy 21.
55FF7.jpg|Fig. 55.7 Phylloid hypomelanosis. This disease is c
haracterized by leaf-like patches of hypopigmentation.
55FT1.jpg|Table 55.1 Molecular reclassification of hereditary ski
n disorders.
55FT2.jpg|Table 55.2 Keratin disorders.
55FT3.jpg|Table 55.3 Hereditary disorders of keratinization.
55FT4.jpg|Table 55.4 Hereditary epidermolysis bullosa (EB).

55FT5.jpg|Table 55.5 Hereditary connective tissue disorders.
aA mutation in the COL3A1 gene has only been reported in one f
amily with hypermobility-type Ehlers-Danlos syndrome. MIDAS, microphthalm
ia, dermal aplasia and sclerocornea
55FT6.jpg|Table 55.6 Ectodermal dysplasias (ED). AEC, ankyloblepharon, ectodermal defects, cleft lip/palate; EEC, ectodermal dysplasia, ectrodactyly, cleft lip/palate.
55FT7.jpg|Table 55.7 Hereditary disorders of hair and nails.
ERCC, excision repair cross-complementing.
55FT8.jpg|Table 55.8 Hereditary disorders of pigmentation.
55FT9.jpg|Table 55.9 Hereditary metabolic skin disorders.
55FT10.jpg|Table 55.10 Hereditary skin disorders characterized by
benign tumors or vascular malformations.
55FT11.jpg|Table 55.11 Hereditary disorders with prominent cutane
ous cancer proneness.
55FT12.jpg|Table 55.12 Hereditary skin disorders with extracutane
ous cancer.
55FT13.jpg|Table 55.13 Other inherited skin disorders. a
 Patients with mutations in XPB, XPD or XPG may have phenoty
pes with features of both xeroderma pigmentosum and Cockayne syndrome (XP/CS; se
e table 55.11). ERCC, excision repair cross-complementing; LAMB, lentigin
es, atrial myxomas, mucocutaneous myxomas, blue nevi; NAME,
nevi, atrial myxomas, myxoid neurofibromas, ephelid
es; LEOPARD, lentigines, ECG changes, ocular hypertelorism,
pulmonary stenosis, abnormal genitalia, retardation of gro
wth, deafness.
55FT14.jpg|Table 55.14 Skin signs associated with chromosomal abe
rrations.
56FF1.jpg|Fig. 56.1 Structure of the epidermis. Inset A. I
n vivo sites of interactions of the major components of the desmosome are sp
eculative; it is not known whether plakophilin mediates the interaction between
desmogleins and desmoplakin or whether it strengthens molecular interactions bet
ween desmoplakin proteins. Inset B: Putative interactions within the hemidesmoso
mes have been determined by in vitro binding assays. Adapted from Borrado
ri and Sonnenberg 1999.
56FF2.jpg|Fig. 56.2 Complex pattern of hair keratin expression in
the human follicle.
56FF3.jpg|Fig. 56.3 Cytokeratin expression.
56FF4.jpg|Fig. 56.4 Aligment and assembly of keratin molecules an
d keratin filament packing.
56FT1.jpg|Table 56.1 Intermediate filaments.
56FT2.jpg|Table 56.2 Keratinocyte integrin receptors.
56FT3.jpg|Table 56.3 Substrate specificity of keratinocyte matrix
metalloproteinases.
56FT4.jpg|Table 56.4 Mutations in keratin genes and associated di
seases. *AD, autosomal dominant; AR, autosomal recessive.
57FF1.jpg|Fig. 57.1 Ichthyosis vulgaris. Fine white scale on
extensor surface of the lower extremity. Courtesy of Anthony J Mancini, M.D.
57FF2.jpg|Fig. 57.2 Hyperlinear palms in ichthyosis vulgaris.
Courtesy of SJ Bale, PhD and JJ DiGiovanna, M.D.
57FF3.jpg|Fig. 57.3 Histology of ichthyosis vulgaris and epidermo
lytic hyperkeratosis. A Ichthyosis vulgaris showing a nearly normal epidermi
s with expanded stratum corneum and reduced granular layer. B Epidermolyt
ic hyperkeratosis with widespread changes of vacuolization of keratinocytes; a p
rominent granular layer with clumped keratohyalin granules is seen.
57FF4.jpg|Fig. 57.4 Steroid sulfatase deficiency. Large dark
brown scale with sparing of the anticubital fossa.
57FF5.jpg|Fig. 57.5 Epidermolytic hyperkeratosis (NPS1 type).
Multiple ridges of hyperkeratosis are seen. Courtesy of SJ Bale, PhD and JJ DiG
iovanna, M.D.
57FF6.jpg|Fig. 57.6 Hyperkeratosis with cobblestone pattern in ep
idermolytic hyperkeratosis. Courtesy of SJ Bale, PhD and JJ DiGiovanna, M.D.
57FF7.jpg|Fig. 57.7 Collodion baby. A Day 1 with ectropion an
d eclabium. B Day 8 with erythema and diffuse mild scaling and misshapen
ears.
57FF8.jpg|Fig. 57.8 Lamellar ichthyosis. Large plate-like sca
les of the lower extremities forming a mosaic pattern.
57FF9.jpg|Fig. 57.9 Congenital ichthyosiform erythroderma. Co
urtesy of SJ Bale, PhD and JJ DiGiovanna, M.D.
57FF10.jpg|Fig. 57.10 Harlequin ichthyosis. Courtesy of SJ Ba
le, PhD and JJ DiGiovanna, M.D.
57FF11.jpg|Fig. 57.11 Netherton syndrome with generalized congeni
tal ichthyosiform erythroderma.
57FF12.jpg|Fig. 57.12 Netherton syndrome. Double-edged scale
of ichthyosis linearis circumflexa.
57FF13.jpg|Fig. 57.13 Abnormal hair shaft in Netherton syndrome. Trichorrhexis invaginata with its ball-and-socket appearance (left arrow) an
d twist in the hair shaft (right arrow).
57FF14.jpg|Fig. 57.14 Sjögren-Larsson syndrome. Scaling
and accentuated skin markings are seen. Courtesy of WB Rizzo, M.D.
57FF15.jpg|Fig. 57.15 Sjögren-Larsson syndrome. Perifove
al glistening white dots of the ocular fundus. Courtesy of WB Rizzo, M.D.
57FF16.jpg|Fig. 57.16 Neutral lipid storage disease. Lipid dr
oplets in circulating granulocytes and monocytes but not lymphocytes or erythroc
ytes. Courtesy of ML Williams, M.D.
57FF17.jpg|Fig. 57.17 Transient erythematous patches of erythroke
ratodermia variabilis.
57FF18.jpg|Fig. 57.18 Erythrokeratodermia variabilis. Fixed h
yperkeratotic plaques.
57FF19.jpg|Fig. 57.19 KID syndrome. Courtesy of L Russell, M.
D. and SJ Bale, PhD.
57FF20.jpg|Fig. 57.20 KID syndrome. Palmar keratoderma with a
grainy surface.
57FF21.jpg|Fig. 57.21 CHILD syndrome. Note the sharp midline
dermacation on the trunk. Courtesy of R Happle, M.D., with permission from S Kar
ger A.G.
57FF22.jpg|Fig. 57.22 Conradi-Hünermann-Happle syndrome. A Erythroderma and linear streaks and whorls of hyperkeratosis. B Epiphy
seal stippling at the knee. A Courtesy of R Happle, M.D. B Courtesy of Jean Bolo
gnia, M.D.
57FT1.jpg|Table 57.1 Features of selected ichthyoses and erythrok
eratodermas.
57FT2.jpg|Table 57.2 Diagnostic clues in the diagnosis of ichthyo
ses and erythrokeratodermas.
57FT3.jpg|Table 57.3 Clinical subtypes of epidermolytic hyperkera
tosis. PS, palm/sole involvement with severe hyperkeratosis; NPS, non-palm/s
ole involvement; +, feature present; –, feature absent. * Palms
, soles and flexures. †Spares palms, soles and face; the areas
most affected are the extremities over joints, back, scalp, periumbilical and pe
riareolar areas. Modified from: DiGiovanna & Bale, Arch Dermatol. 1994;130:1
026–35.
57FT4.jpg|Table 57.4 Neonatal presentation of selected ichthyoses
and related disorders. *Some attenuated or band-like involvement
may occasionally be appreciated on the contralateral side.
57FT5.jpg|Table 57.5 Differential diagnosis of collodion baby.
58FF1.jpg|Fig. 58.1 Structural organization of connexin channels
and model of a gap junction plaque. Six connexin molecules oligomerize to fo
rm a hemichannel with a central pore that has a maximum diameter of 2 nm. C
onnexins may be homomeric if all the participating molecules are of the same con
nexin species, or heteromeric if they differ. Connexins of adjacent cells dock i
n the intercellular gap to form a complete gap junction intercellular channel. R
edrawn with permission from Richard.7
58FF2.jpg|Fig. 58.2 Diffuse non-epidermolytic palmoplantar kerato
sis.
58FF3.jpg|Fig. 58.3 Focal palmoplantar keratosis of the striate t
ype on the palm. Courtesy of Andrew Lin, M.D.
58FF4.jpg|Fig. 58.4 Diffuse epidermolytic palmoplantar keratosis
with diffuse hyperkeratosis.
58FF5.jpg|Fig. 58.5 Pathology of non-epidermolytic palmoplantar k
eratosis. Note the massive hyperkeratosis, acanthosis and hypergranulosis.
58FF6.jpg|Fig. 58.6 Vohwinkel's mutilating syndrome. (A) Diffuse keratoderma of the palms with (B) pseudoainhum formation.
58FF7.jpg|Fig. 58.7 Bart–Pumphrey syndrome. Leukonychia
and knuckle pads, with sensorineural deafness.
58FF8.jpg|Fig. 58.8 Papillon-Lefèvre syndrome. Plantar k
eratoderma. Courtesy of Yale Residents Slide Collection.
58FF9.jpg|Fig. 58.9 Focal PPK in association with carcinoma of th
e esophagus.
58FF10.jpg|Fig. 58.10 Dendritic keratitis in a patient with Richn
er–Hanhart syndrome. Courtesy of Alex Levin, M.D.
58FF11.jpg|Fig. 58.11 Richner–Hanhart syndrome (tyrosinemia
II). Focal painful keratoses on the plantar surface in a patient with corne
al ulcers and mental retardation. Courtesy of Jean Bolognia, M.D.
58FF12.jpg|Fig. 58.12 Pachyonychia congenita with thickening of p
almar skin. Note wedge-shaped subungual hyperkeratosis.
58FF13.jpg|Fig. 58.13 Punctate keratoses of the palmar creases in
an African-American.
58FF14.jpg|Fig. 58.14 Focal acrokeratoelastoides. Multiple sk
in-colored papules at the margin of the palmar skin. Courtesy of Yale Residents
Slide Collection.
58FT1.jpg|Table 58.1 Palmoplantar keratodermas (PPK). *PPK is
a major feature of the disorder.
58FT2.jpg|Table 58.2 Hereditary palmoplantar keratodermas (PPK) a
nd their genetic bases. *Less confirmed. NEPPK, non-epidermolytic PPK; EPPK,
epidermolytic PPK; EHK, epidermolytic hyperkeratosis; PC, pachyonychia congenit
a.
58FT3.jpg|Table 58.3 Human connexin disorders. Adapted from R
ichard7 with permission. OMIM, On-line Mendelian Inheritance in Man.
www.nchi.nlmnih.gov/Omim/searchomim.html.
59FF1.jpg|Fig. 59.1 Cellular sites of calcium pumps. Calcium
pumps ATP2A2 and ATP2C1. PIP2, phospho-inositol diphosphate; IP3
, inositol triphosphate; PLC, phospholipase C; DAG, diacylglycerole; PKC,
proteinkinace C;
59FF2.jpg|Fig. 59.2 Darier's disease. Keratotic brown papules
on the chest becoming confluent between the breasts.
59FF3.jpg|Fig. 59.3 Darier's disease. Truncal involvement in
seborrheic areas.
59FF4.jpg|Fig. 59.4 Darier's disease. Crusted papules at the
hair margin of the face.
59FF5.jpg|Fig. 59.5 Distribution patterns for Darier's, Hailey&#8
211;Hailey and Grover's disease.
59FF6.jpg|Fig. 59.6 Darier's disease. Multiple flat-topped pa
pules on the dorsae of the hands.
59FF7.jpg|Fig. 59.7 Darier's disease. Severe involvement in i
ntertriginous zones, including the groin, submammary area and abdominal fold.
59FF8.jpg|Fig. 59.8 Palmar involvement Darier's disease. Palm
ar papules. Both keratotic papules and keratin filled depressions are seen. Cour
tesy of Kalman Watsky, M.D.
59FF9.jpg|Fig. 59.9 Darier's disease. Nail changes with longi

tudinal erythronychia and notching of the free edge of the nail plate.
59FF10.jpg|Fig. 59.10 Darier's disease. Mucosal whitish papul
es on the palate.
59FF11.jpg|Fig. 59.11 Darier's disease with superimposed HSV infe
ction (Kaposi's varicelliform eruption). Multiple hemorrhagic crusts of a si
milar size are seen.
59FF12.jpg|Fig. 59.12 Type 1 segmental Darier's disease. Note
the distribution of the papules along Blaschko's lines.
59FF13.jpg|Fig. 59.13 Histopathology of Darier's disease. Hyp
erkeratosis, grains, corp ronds and acantholysis leading to suprabasilar cleftin
g are seen.
59FF14.jpg|Fig. 59.14 Acrokeratosis verruciformis of Hopf. Ex
clusive involvement of the dorsal aspects of the hands with flat-topped papules.
59FF15.jpg|Fig. 59.15 Hailey–Hailey disease. Erythemato
us plaque in the axilla with an active border.
59FF16.jpg|Fig. 59.16 Hailey–Hailey disease. Erythemato
us plaque with erosions and maceration of the inguinal canal and scrotum.
59FF17.jpg|Fig. 59.17 Hailey–Hailey disease. Flaccid ve
sicles and erosions.
59FF18.jpg|Fig. 59.18 Hailey–Hailey disease. Chronic su
bmammary lesions with erosions and crusting.
59FF19.jpg|Fig. 59.19 Histopathology of Hailey–Hailey disea
se. Suprabasilar as well as more widespread acantholysis within the epidermi
s (right-hand side). The latter has been likened to a ‘dilapidated brick w
all’.
60FF1.jpg|Fig. 60.1 Ataxia–telangiectasia. Extensive te
langiectasia on the neck of a 20-year-old woman with ataxia–telangiectasia
.
60FF2.jpg|Fig. 60.2 Persistent granulomatous plaques on the leg o
f child with ataxia–telangiectasia. These lesions often ulcerate and a
re difficult to manage.
60FF3.jpg|Fig. 60.3 Chronic mucocutaneous candidiasis. Extens
ive, recalcitrant thrush on the tongue of a 5-year-old with chronic mucocutaneou
s candidiasis.
60FF4.jpg|Fig. 60.4 Chronic mucocutaneous candidiasis. Marked
onychodystrophy with significant paronychial swelling and erythema in a young b
oy with chronic mucocutaneous candidiasis.
60FF5.jpg|Fig. 60.5 Chédiak–Higashi syndrome. Ligh
t microscopic examination of hair shows giant melanosomes in patients with Ch&#2
33;diak–Higashi syndrome.
60FF6.jpg|Fig. 60.6 The main components and effector actions of c
omplement. The C3b bound to the C3 convertase binds C5, allowing the C3 conv
ertase to generate C5b, which associates with the bacterial membrane and trigger
s the late events. Adapted with permission from Janeway CA, Travers P, Walport M
, Shlomchik M. Immunobiology. 5th edition. London: Harcourt.
60FF7.jpg|Fig. 60.7 Swollen, erythematous draining inguinal lymph
adenopathy related to Staphylococcus aureus infection in a boy with chron
ic granulomatous disorder. Courtesy of A Ammann, MD; Reprinted with permissi
on from Schachner L, Hansen R, eds. Pediatric Dermatology.
60FF8.jpg|Fig. 60.8 Hyperimmunoglobulin E syndrome. Infant wi
th hyperimmunoglobulin E syndrome shows several erythematous, slightly purulent
‘cold’ abscesses on the forehead and scalp.
60FF9.jpg|Fig. 60.9 Hyperimmunoglobulin E syndrome. Coarse fa
ces with scattered small staphylococcal pustules on a 9-year-old boy with hyperi
mmunoglobulin E syndrome. Reprinted with permission from Schachner L, Hansen R,
eds. Pediatric Dermatology.
60FF10.jpg|Fig. 60.10 Leukocytoclastic vasculitis on the legs of
a girl with common variable immunodeficiency. Autoimmune disorders show a si
gnificant increase in frequency. Reprinted with permission from Schachner L, Han
sen R, eds. Pediatric Dermatology. © Churchill Livingstone, 1995.

60FF11.jpg|Fig. 60.11 Extensive, recalcitrant warts in an adult w
ith hyperimmunoglobulinemia M syndrome. Reprinted with permission from Schac
hner L, Hansen R, eds. Pediatric Dermatology. © Churchill Livingstone, 1995
.
60FF12.jpg|Fig. 60.12 Painful oral ulceration in a patient with h
yperimmunoglobulinemia M syndrome. Reprinted with permission from Schachner
L, Hansen R, eds. Pediatric Dermatology. © Churchill Livingstone, 1995.
60FF13.jpg|Fig. 60.13 A 7-year-old boy with leukocyte adhesion de
ficiency type I was scratched by his sister, resulting in a large gaping wound t
hat healed poorly. Reprinted with permission from Schachner L, Hansen R, eds
. Pediatric Dermatology. © Churchill Livingstone, 1995.
60FF14.jpg|Fig. 60.14 Severe atopic dermatitis in an infant with
Wiskott–Aldrich syndrome. The boy was successfully treated with bone m
arrow transplantation, and his dermatitis virtually cleared owing to the T-cell
engraftment. Reprinted with permission from Schachner L, Hansen R, eds. Pediatri
c Dermatology. © Churchill Livingstone, 1995.
60FT1.jpg|Table 60.1 Screening laboratory tests for a patient wit
h recurrent cutaneous infections (including staphylococcal) where there is suspi
cion of a primary immunodeficiency.
60FT2.jpg|Table 60.2 Subgroups of chronic mucocutaneous candidias
is in children and adolescents.
60FT3.jpg|Table 60.3 Complement disorders. Adapted with permi
ssion from Schachner L, Hansen R, eds. Pediatric Dermatology
60FT4.jpg|Table 60.4 Proteins of the classical pathway of complem
ent activation. With permission from Janeway CA, Travers P, Walport M, Shlom
chik M. Immunobiology. 5th edition. London, Harcourt.
60FT5.jpg|Table 60.5 Features of systemic lupus erythematosus (SL
E) in C2 deficiency. Adapted with permission from Schachner L, Hansen R, eds
. Pediatric Dermatology
60FT6.jpg|Table 60.6 Frequency of signs and symptoms in patients
with chronic granulomatous disease.
60FT7.jpg|Table 60.7 Classification of severe combined immunodefi
ciency. Adapted with permission from Schachner L, Hansen R, eds. Pediatric D
ermatology. © Churchill Livingstone, 1995.
61FF1.jpg|Fig. 61.1 The neurofibromatosis 1 gene and neurofibromi
n. NF1 is located on chromosome 17q11.2 and encodes for the GAP-relat
ed protein neurofibromin. One of the functions of neurofibromin is to negatively
regulate the activity of RAS proteins. RAS, like other related G proteins, is d
ependent upon GTP binding for its full activity, and GAP proteins shut off the s
ignal by accelerating the hydrolysis of GTP to GDP.
61FF2.jpg|Fig. 61.2 Café-au-lait macule and axillary freckli
ng. An oval-shaped light-brown patch is present in the axilla of this child
along with multiple small 1–2 mm lentigines (Crowe's sign).
61FF3.jpg|Fig. 61.3 Cutaneous neurofibromas. Small, soft, ski
n-colored to pink polypoid neurofibromas that characterize NF1. Reproduced with
permission from Tsao H. Update on familial cancer syndromes and the skin. J Am A
cad Dermatol. 2000;42:939–69.
61FF4.jpg|Fig. 61.4 Plexiform neurofibroma. Soft tissue swell
ing of the left hand from a plexiform neurofibroma. Note the overlying hyperpigm
entation.
61FF5.jpg|Fig. 61.5 NF1 A common location for NFs in women is
the areola. Note the numerous lentigines on the breast. Courtesy of Yale Reside
nts Slide Collection.
61FF6.jpg|Fig. 61.6 Lisch nodules. Multiple yellow-brown papu
les of the iris. Courtesy of Yale Residents Slide Collection.
61FF7.jpg|Fig. 61.7 Development of clinical features in neurofibr
omatosis. The time course of major diagnostic lesions that develop in NF1. D
uring the first few years of life a child may have only café-aulait macules
(CALMs). A single criterion is insufficient to make a definitive diagnosis of N
F1, and so these patients would be considered ‘NF1 suspects’.

61FF8.jpg|Fig. 61.8 Plexiform neurofibroma. Photomicrograph o
f plexiform neurofibroma. Courtesy of Yale Residents Slide Collection.
61FF9.jpg|Fig. 61.9 Approach to the young child with six or more
café-au-lait macules. Most patients will eventually prove to have NF1 o
r, less often, one of the other CALM-associated syndromes. Although rare, the la
tter should be considered if other NF1 signs do not occur. Adapted from Korf .
61FF10.jpg|Fig. 61.10 The TSC genes and their protein prod
ucts. TSC1 and TSC2 are located on chromosomes 9q34 and 16p13,
respectively. The TSC1 product hamartin interacts with the TSC2 p
roduct tuberin and negatively regulates signaling by the small GTPase, Rab. Like
Ras, Rab activity is dependent upon bound GTP, and tuberin, like neurofibromin,
accelerates hydrolysis of GTP to GDP in order to turn off Rab.
61FF11.jpg|Fig. 61.11 Development of the cutaneous features assoc
iated with tuberous sclerosis. Hypomelanotic macules are usually the only cu
taneous finding at birth.
61FF12.jpg|Fig. 61.12 Ash leaf macule in a child with tuberous sc
lerosis. Courtesy of Yale Residents Slide Collection.
61FF13.jpg|Fig. 61.13 Guttate leukoderma of tuberous sclerosis. Multiple 1–2 mm hypopigmented ‘confetti’ macules on th
e forearm. Courtesy of Yale Residents Slide Collection.
61FF14.jpg|Fig. 61.14 Facial angiofibromas of tuberous sclerosis. Multiple shiny, dome-shaped papules on the cheeks and nose in an adolescent
(A) and an adult (B). There is also a fibrous plaque on the lower
cheek (A). Courtesy of Yale Residents Slide Collection.
61FF15.jpg|Fig. 61.15 Fibrous plaque of the forehead in a patient
with tuberous sclerosis. The plaque is firm to palpation. Courtesy of Yale
61FF16.jpg|Fig. 61.16 Shagreen patch on the lower back. The s
urface of this connective tissue nevus is said to resemble pig skin. Courtesy of
61FF17.jpg|Fig. 61.17 Periungual fibromas of tuberous sclerosis. Multiple fibromas of the toes arising in a periungual location. Courtesy of
61FF18.jpg|Fig. 61.18 Retinal hamartomas of tuberous sclerosis. Courtesy of Yale Residents Slide Collection.
61FF19.jpg|Fig. 61.19 Cranial CT demonstrating multiple calcified
subependymal nodules in a paraventricular location. Courtesy of Yale Reside
61FT1.jpg|Table 61.1 Neurofibromatosis subtypes.
61FT2.jpg|Table 61.2 Major clinical features of neurofibromatosis
type 1. JXGs, juvenile xanthogranulomas.
61FT3.jpg|Table 61.3 Diagnostic criteria for neurofibromatosis ty
pe 1. With permission from NIH Conference: Neurofibromatosis Statement. Arch
Neurol 1988;45:575–8.
61FT4.jpg|Table 61.4 Disorders associated with multiple café
-au-lait macules. AD, autosomal dominant; AN, acanthosis nigricans; AR, auto
somal recessive; LEOPARD, lentigines/ECG abnormalities/ocular hypertelorism/pulm
onary stenosis/abnormalities of genitalia/retardation of growth/deafness syndrom
e; MR, mental retardation; CALMs, café-au-lait macules. *Some fa
mily members can have Lisch nodules, macrocephaly, and even neurofibromas; given
linkage to 17q, may be allelic to NF1 gene or there is a series of genes at thi
s site. †Estimates of incidence94. §
To date, observed in a single family. ¶Single case reports of multiple CALM
s in association with X-linked hypohidrotic ectodermal dysplasia, woolly hair, a
nd osteoma cutis.
61FT5.jpg|Table 61.5 Major clinical features of tuberous sclerosi
s. *Increasingly difficult to distinguish from normal myocardium as patient
ages.
61FT6.jpg|Table 61.6 Diagnostic criteria for tuberous sclerosis c
omplex. For example, liver or spleen carcinomas.

61FT7.jpg|Table 61.7 Evaluation and management of tuberous sclero
sis patients.
62FF1.jpg|Fig. 62.1 Blaschko’s lines. A These di
agrams are taken from Blaschko’s drawings1. B Blaschko&#
8217;s lines on the face, based on personal observation and ref. 1. C Bla
schko’s lines on the jawline and neck, based on personal observations and
ref. 1. D Blaschko’s lines on the scalp9. E Blasc
hko’s lines on the genitalia, based on ref. 1.
62FF2.jpg|Fig. 62.2 Linear cutaneous lesions that can follow Blas
chko's lines.
62FF3.jpg|Fig. 62.3 Function of NEMO. In IP, lack of NFκ
B essential modulator (NEMO) results in failure to activate NFκB, which nor
mally protects against TNF-induced apoptosis.
62FF4.jpg|Fig. 62.4 Incontinentia pigmenti. A Stage 3 (hyperp
igmented streaks). The scalloped edges of the lesions are consistent with growth
of normal keratinocytes into the damaged areas. B Stage 4 (atrophic, hyp
opigmented lesions on the leg).
62FF5.jpg|Fig. 62.5 Goltz's syndrome. A Streaks of vermiculat
e atrophy (hypopigmented) and fat herniation/hamartoma in a girl with Goltz's sy
ndrome. B Telangiectasia. Courtesy of Yale Residents Slide Collection.
62FF6.jpg|Fig. 62.6 Epidermolytic verrucous epidermal nevus.
Note the shedding of scale within several of the lesions. Courtesy of Yale Resid
ents Slide Collection.
62FF7.jpg|Fig. 62.7 Linear Darier's disease with hyperpigmented,
keratotic papules. Courtesy of Yale Residents Slide Collection.
62FF8.jpg|Fig. 62.8 Linear psoriasis. Erythema and scale are
seen within the streak as well as in scattered discoid lesions. Courtesy of Yale
62FF9.jpg|Fig. 62.9 Linear lichen planus. More active lesions
are seen on the calf while post-inflammatory hyperpigmentation predominates on
the thigh.
62FF10.jpg|Fig. 62.10 Extensive epidermal nevus. The lesions
on the neck are more verrucous. Courtesy of Yale Residents Slide Collection.
62FF11.jpg|Fig. 62.11 Epidermal nevus with the classic V-shaped p
attern seen on the mid back.
62FF12.jpg|Fig. 62.12 Inflammatory linear verrucous epidermal nev
us. Scaly psoriasiform plaques are in a linear array.
62FT1.jpg|Table 62.1 Causes of mosaicism and the corresponding pa
thogenesis4.
62FT2.jpg|Table 62.2 Mosaic skin conditions classified according
to the nature of the generalized condition.
62FT3.jpg|Table 62.3 Expected distribution of lesions caused by m
osaic skin genes, according to timing and mechanism of mosaicism.
62FT4.jpg|Table 62.4 Expected pattern of cutaneous mosaicism acco
rding to cell type or tissue.
62FT5.jpg|Table 62.5 Additional manifestations of incontinentia p
igmenti (IP).
62FT6.jpg|Table 62.6 Changes in zygosity causing mosaicism for au
tosomal traits.
63FF1.jpg|Fig. 63.1 Multiple endocrine neoplasia type 1. Mult
iple connective tissue nevi in a patient with MEN type 1.
63FF2.jpg|Fig. 63.2 Multiple endocrine neoplasia type II. Enl
arged lips and multiple mucosal neuromas on the tongue of a patient with MEN 2b.
63FF3.jpg|Fig. 63.3 Multiple mucosa. Colored papules on the t
ongue in a patient with Cowden's disease.
63FF4.jpg|Fig. 63.4 Gardner syndrome. Note the epidermoid cys
t at the base of the second toe.
63FF5.jpg|Fig. 63.5 Congenital hypertrophy of retinal pigment epi
thelium. Courtesy of L Tychsen, M.D.
63FF6.jpg|Fig. 63.6 Muir–Torre syndrome with multiple sebac

eous neoplasms. Courtesy of Dan Ring, M.D.
63FF7.jpg|Fig. 63.7 Clinical features of alkaptonuria.
63FF8.jpg|Fig. 63.8 Differential diagnosis of ‘nutritional
dermatitis’.
63FF9.jpg|Fig. 63.9 Clinical features of Fabry disease and fucosi
dosis. The insert shows angiokeratoma corporis diffusum in a patient with Fa
bry disease. (Photograph courtesy of Anthony J Mancini, MD.)
63FF10.jpg|Fig. 63.10 Phenylketonuria. Infant with PKU and sc
lerodermoid skin changes. Courtesy of the New York Medical College.
63FF11.jpg|Fig. 63.11 Werner's syndrome. Characteristic featu
res include a beaked nose, tautness of the skin, prominent veins and micrognathi
a. Courtesy of Ron Rapini, M.D.
63FF12.jpg|Fig. 63.12 Kindler's syndrome. Atrophy, erosions a
nd fusion of toes (fourth and fifth toes) in an infant (A); poikiloderma
of the face and neck with ‘skip’ areas (B); wrinkling due to
atrophy and fusion between the fourth and fifth toes (C). (C, Courtesy of
Jean Bolognia, M.D.)
63FF13.jpg|Fig. 63.13 Male patients with hypohidrotic ectodermal
dysplasia. Note the flat nasal bridge, depressed nasal tip, sparse hair (sca
lp, eyebrows, eyelashes), peg-shaped teeth, full lips and sebaceous hyperplasia.
Also note the normal secondary hair in adults. D Courtesy of Mary Williams, M.D
.
63FF14.jpg|Fig. 63.14 Female patients with hypohidrotic ectoderma
l dysplasia. Note the peg-shaped teeth, hypodontia, periorbital hyperpigment
ation and sebaceous hyperplasia.
63FF15.jpg|Fig. 63.15 Hidrotic ectodermal dysplasia (Clouston). Note the thickened nails and thin hair in a young adult.
63FF16.jpg|Fig. 63.16 Ankyloblepharon-ectodermal dysplasia-clefti
ng syndrome. A Thick scale-crust of the scalp and alopecia. B Strands
of tissue between the eyelids. Courtesy of Jean Bolognia, M.D.
63FF17.jpg|Fig. 63.17 Rapp–Hodgkin syndrome.
63FF18.jpg|Fig. 63.18 Ectodermal dysplasia-ectrodactyly-clefting
syndrome. Note the characteristic split–hand and split–feet defo
rmities.
63FF19.jpg|Fig. 63.19 Tooth and nail (Witkop) syndrome. Prolo
nged retention of primary teeth in an 11-year old.
63FT1.jpg|Table 63.1 Genodermatoses. See also Chapter 55. *Di
scussed in this chapter.
63FT2.jpg|Table 63.2 Types of multiple endocrine neoplasia. A
D, autosomal dominant; CALM, café-au-lait macules. a Tumor suppr
essor gene. b Rearranged during transfection of proto-oncogene; same
gene responsible for Hirschsprung disease and familial medullary thyroid carcino
ma. c Induce dimerization and activation of receptor in the absence o
f its ligand. dMeasurement of serum calcitonin level after calcium or
pentagastrin injection. eOnset usually prior to medullary thyroid ca
rcinoma.
63FT3.jpg|Table 63.3 Clinical manifestations of Bannayan–Ri
ley–Ruvalcaba syndrome and Cowden disease. a Trichilemmomas
and verrucae. b Includes lips and tongue. cUnusual. 
d Only a few patients with Cowden disease. eIncludes accelerate
d growth of the first metacarpal and first and second middle phalanges, syndacty
ly and brachydactyly. Reproduced with permission from Fargnoli MC et al. Clinico
pathological findings in the Bannayan-Riley-Ruvalcaba syndrome. Arch Dermatol 19
96;132:1214–18. © American Medical Association.
63FT4.jpg|Table 63.4 International Cowden Syndrome Consortium ope
rational criteria, 2000
63FT5.jpg|Table 63.5 Inherited metabolic disorders associated wit
h angiokeratoma corporis diffusum. MR, mental retardation; AR, autosomal rec
essive; XL, X-linked recessive.
63FT6.jpg|Table 63.6 Cutaneous manifestations of mitochondrial re

spiratory chain disorders
63FT7.jpg|Table 63.7 Differential diagnosis of progeria and relat
ed disorders. AD, autosomal dominant; AR, autosomal recessive.
63FT8.jpg|Table 63.8 The most common ectodermal dysplasias. E
D, ectodermal dysplasia; EEC, ectodermal dysplasia-ectrodactyly-clefting; AEC, a
nkyloblepharonectodermal dysplasia-clefting; XLR, X-linked recessive; AR, autoso
mal recessive; AD, autosomal dominant; GU, genitourinary.
64FF1.jpg|Fig. 64.1 Intermittent/multisite pattern of neural tube
closure in humans. The five separate initiation sites are labeled (in chron
ological order, 1–5), and the direction of neural tube closure is indicate
d by the arrows. The 2–3 junction corresponds to the location of frontoeth
moidal neural tube defects, the 2–4 junction to parietal defects, and the
1–4 junction to occipital defects. Closure in region 4 is thought to occur
via membranous growth, proceeding in a superior direction; incomplete closure a
t this site could therefore result in a membranous defect at the 2–4 junct
ion (i.e. the vertex).
64FF2.jpg|Fig. 64.2 Common sites of developmental anomalies of th
e face and neck. This schematic depicts the common sites of developmental an
omalies of the face and neck.
64FF3.jpg|Fig. 64.3 Hair collar sign. Membranous aplasia cuti
s congenita with a hair collar and an associated capillary malformation. Courtes
y of Kalman L Watsky, M.D.
64FF4.jpg|Fig. 64.4 Hair collar sign. Membranous aplasia cuti
s congenita with a bullous appearance and a surrounding hair collar.
64FF5.jpg|Fig. 64.5 Differential diagnosis and evaluation of a po
sitive hair collar sign. Computed tomography (CT) is the most accurate metho
d of detecting skull defects and, in general, a more readily available study. Ho
wever, if a bony defect is detected by CT, a follow-up evaluation by magnetic re
sonance imaging (MRI) may be indicated to better determine whether there is exte
nsion of soft tissue transcranially.
64FF6.jpg|Fig. 64.6 Dermoid cyst. This dermoid cyst presented
in an infant as a firm subcutaneous nodule superior to the lateral left eyebrow
. Courtesy of Kalman L Watsky, M.D.
64FF7.jpg|Fig. 64.7 Spectrum of cranial neural tube defects.
64FF8.jpg|Fig. 64.8 Approach to patients with cutaneous signs of
spinal dysraphism.
64FF9.jpg|Fig. 64.9 Midline deep sacral dimple. The dimple wa
s located above the gluteal cleft in association with a small tail. Courtesy of
Seth J Orlow, M.D., PhD, New York, N.Y.
64FF10.jpg|Fig. 64.10 Circumscribed midline hypertrichosis overly
ing the lower thoracic spine in a patient with occult dysraphism. The patien
t periodically clips the distal ends. Courtesy of Jean L Bolognia, M.D.
64FF11.jpg|Fig. 64.11 Midline ulcerated superficial hemangioma ov
erlying the sacral spine. This infant had an underlying diastematomyelia. Co
urtesy Anthony J Mancini, M.D.
64FF12.jpg|Fig. 64.12 Aplasia cutis congenita. Atrophic cutan
eous defect extending from the lateral eyebrow to the anterior hairline in a pat
ient with Setleis syndrome. Note the upward-slanting eyebrows and ‘leonine
’ facial appearance. Courtesy of Seth Orlow, M.D., PhD.
64FF13.jpg|Fig. 64.13 Preauricular skin defects. Multiple dis
crete, round, atrophic skin defects in an infant, extending from the scalpline t
oward the angle of the mouth in a strikingly linear arrangement. Courtesy of Jea
n L Bolognia, M.D.
64FF14.jpg|Fig. 64.14 Aplasia cutis congenita. ACC resulting
from congenital varicella. Note the sharply demarcated, deep ulcer on the lower
abdominal wall.
64FF15.jpg|Fig. 64.15 Accessory tragi. Multiple skin-colored
papulonodules in a typical preauricular location as well as on the mandibular ch
eek.
64FF16.jpg|Fig. 64.16 ‘Milk lines’. Supernumerary

nipples and other forms of accessory mammary tissue represent focal remnants of
the embryologic mammary ridges that extend from the anterior axillary fold to t
he upper medial thigh bilaterally.
64FF17.jpg|Fig. 64.17 Supernumerary nipple. Note the supernum
erary nipple with a surrounding areola in a typical location on the inframammary
chest. Courtesy of Jean L Bolognia, M.D.
64FF18.jpg|Fig. 64.18 Bilateral rudimentary supernumerary digits. The ulnar side of the fifth digit is the most common location.
64FF19.jpg|Fig. 64.19 Amniotic band syndrome. Numerous circum
ferential grooves on the upper and lower extremities bilaterally, resulting from
amniotic bands. Courtesy of Leo Litter, M.D.
64FT1.jpg|Table 64.1 Skin lesions of the spinal axis associated w
ith dysraphism. *Due to a potential risk of meningitis, these lesions should
not be probed.
64FT2.jpg|Table 64.2 Classification scheme for aplasia cutis cong
enita. ACC, aplasia cutis congenita; AD, autosomal dominant; AR, autosomal r
ecessive; CNS, central nervous system; EB, epidermolysis bullosa. Adapted from F
rieden IJ, J Am Acad Dermatol 1986;14:646–60. Bold text in column 4 signif
ies main topics, followed by details.
64FT3.jpg|Table 64.3 Syndromes associated with aplasia cutis cong
enita (ACC, group 9). ACC also may be found in patients with focal dermal hy
poplasia (Goltz syndrome), branchio-oculo-facial syndrome, and several types of
ectodermal dysplasias, including the EEC syndrome (ectrodactyly, ectodermal dysp
lasia, clefting), AEC syndrome (ankyloblepharon, ectodermal dysplasia, cleft lip
/palate; Hay–Wells syndrome) and tricho-odonto-onychial dysplasia. In addi
tion, there have been reports of scalp ACC in patients with Pallister–Kill
ian syndrome (tetrasomy 12p), Opitz syndrome, popliteal pterygium syndrome, Mars
hall syndrome and hereditary sensory and motor neuropathy type I (www.ncbi.nlm.n
ih.gov/OMIM). *Along the embryonic fusion line between the frontonasa
l prominence and the maxillary prominence of the first branchial arch. &#82
24;Along the embryonic fusion line between the maxillary and mandibular pr
ominences of the first branchial arch.
64FT4.jpg|Table 64.4 Diseases affecting the skin that are associa
ted with cleft lip and/or palate. Other disorders associated with cleft lip/
palate that also can affect the skin include Cornelia de Lange, Roberts, Simpson
–Golabi–Behmel and Pallister–Hall syndromes, oculo-auriculo-ve
rtebral dysplasia, Meige disease (familial lymphedema praecox) and trisomy 13. A
D, autosomal dominant; AR, autosomal recessive; X-D, X-linked dominant. * Can be caused by mutations in the p63 gene. † Includes Zlo
togora–Ogur syndrome, Rosselli–Gulienetti syndrome and Margarita Isl
and ectodermal dysplasia. ¶Thought to be allelic.
64FT5.jpg|Table 64.5 Diseases affecting the skin that are associa
ted with congenital digital anomalies. Other disorders associated with digit
al anomalies that also may affect the skin include Cornelia de Lange, Roberts, S
impson–Golabi–Behmel, Pallister–Hall, Russel–Silver, Rub
instein–Taybi and Hurler syndromes, trisomy 13, Fanconi anemia and the Pol
and anomaly. CMTC, cutis marmorata telangiectatica congenita; AD, autosomal domi
nant; AR, autosomal recessive; syndactyly, fused digits; ectrodactyly, absent di
gits (e.g. ‘split hand’ or ‘lobster claw’); polydactyly,
extra digits; clinodactyly, laterally or medially ‘bent’ digits; br
achydactyly, short digits. *Can be caused by mutations in the p63 gen
e; allelic disorders with overlapping manifestations (e.g. ectrodactyly, nipple
hypo-/aplasia) include ADULT (acro-dermato-ungual-lacrimal-tooth) syndrome and l
imb-mammary syndrome. †Patients often have macrodactyly.
65FF1.jpg|Fig. 65.1 Migration of melanocytes from the neural cres
t. Melanocytes migrate to the uveal tract, the leptomeninges, and the cochle
a, as well as the epidermis and hair follicle. The retina actually represents an
outpouching of the neural tube.
65FF2.jpg|Fig. 65.2 Binding of steel factor to the KIT receptor o
n melanocytes. Because the KIT receptor is a tyrosine kinase receptor, it ha

s the ability to place phosphate groups on the tyrosine residues of other protei
ns (as well as itself). Genetic mutations in the KIT gene that prevent th
e activation of the KIT receptor by steel factor lead to piebaldism, whereas act
ivating mutations in the KIT gene are seen in adult patients with mastocy
tosis and mast cell leukemia.
65FF3.jpg|Fig. 65.3 Receptor–ligand interactions required f
or the survival and migration of neural crest-derived cells. In the developi
ng central nervous system, endothelin B receptors (EDNRB) on melanoblast-ganglio
n cell precursors interact with endothelin-3 (EDN3), and in the mesenchyme and f
inal destination sites, KIT receptors on melanoblasts and melanocytes interact w
ith steel factor.
65FF4.jpg|Fig. 65.4 A melanocyte residing in the basal layer of t
he epidermis. In normal skin, approximately every tenth cell in the basal la
yer is a melanocyte. Melanosomes are transferred from the dendrites of the melan
ocyte into neighboring keratinocytes of the epidermis, hair matrices and mucous
membranes; no transfer occurs in the pigmented epithelium of the retina.
65FF5.jpg|Fig. 65.5 An epidermal sheet following incubation with
5 mM l-DOPA for 4–5 hours. The melanocytes t
urn black because they contain the enzyme tyrosinase, which converts DOPA to bla
ck DOPA-melanin. Note the multiple dendrites and regular spacing of the melanocy
tes.
65FF6.jpg|Fig. 65.6 Formation of a melanosome. After glycosyl
ation within the Golgi apparatus, several of the enzymes involved in the formati
on of melanin (including tyrosinase) are packaged in vesicles and then combine w
ith the matrix proteins. As more melanin is deposited within the melanosomes, th
ey migrate into the dendrites in preparation for their transfer into neighboring
keratinocytes. In some patients with OCA1, tyrosinase polypeptides become &#821
6;trapped’ within the lumen of the RER (*) and are never incorporated into
melanosomes. T, tyrosinase; RER, rough endoplasmic reticulum; and SER, smooth e
ndoplasmic reticulum.
65FF7.jpg|Fig. 65.7 Shuttling of proteins within the cell followi
ng translation and post-translational modifications. After such modification
s, e.g. addition of sugar residues in the ER and Golgi apparatus, proteins must
be shuttled to the correct cellular location, either a specific intracytoplasmic
organelle or the plasma membrane. Adaptor proteins (AP3) function as regulators
of this protein sorting and, in the case of tyrosinase, specific dileucine resi
dues in its cytoplasmic tail aid in the sorting. Mutations in the gene that enco
des the β3A subunit of AP3 lead to one form of Hermansky–Pudlak syndr
ome.
65FF8.jpg|Fig. 65.8 Descriptions and electron photomicrographs of
the four major stages of eumelanin melanosomes.
65FF9.jpg|Fig. 65.9 The melanin biosynthetic pathway. The pat
hway includes demonstration of the sites of dysfunction in OCA1 (tyrosinase), OC
A3 (TRP1), and rufous OCA (TRP1). The two major forms of melanin in the skin and
hair are brown–black eumelanin and yellow–red pheomelanin. DHI, 5,6
-dihydroxyindole; DHICA, 5,6-dihydroxyindole-2-carboxylic acid; DOPA, dihydroxyp
henylalanine; MW, molecular weight; TRP, tyrosinase-related protein. Courtesy of
Dr Vincent Hearing.
65FF10.jpg|Fig. 65.10 Proposed model for the arrangement of the P
protein within the lipid bilayer. The polypeptide has 12 putative transmemb
rane domains. Adapted from Rinchik et al18, with permission of Macmil
lan Magazines Ltd.
65FF11.jpg|Fig. 65.11 Transmembrane proteins of the melanosome. The transmembrane locations of several key proteins are shown. Note the short
cytoplasmic tails. In humans and mice, TRP1 stabilizes tyrosinase and in mice,
it also functions as DHICA oxidase. The antibody HMB45 recognizes pmel-17, also
known as the silver protein, and the antibody mel-5 recognizes TRP1. DHI, 5,6-di
hydroxyindole; DHICA, 5,6-dihydroxyindole-2-carboxylic acid; LAMP, lysosomal-ass
ociated membrane protein; TRP, tyrosinase-related protein.
65FF12.jpg|Fig. 65.12 Causes of increased melanin production.

This can result from activation of protein kinase A or C as well as exposure to
growth factors such as basic fibroblast growth factor (bFGF) or ultraviolet (UV
) irradiation. UV irradiation can lead to an increase in the number and activity
of MC1-R on melanocytes, the expression of POMC and its derivative peptides (e.
g. MSH) by keratinocytes and other cells within the dermis, and the production o
f endothelin-1 by keratinocytes.
65FF13.jpg|Fig. 65.13 Post-translational processing of the POMC p
olypeptide. ac, acetylated; ACTH, adrenocorticotropic hormone; des, desacety
l; END, endorphin; LPH, lipotropic hormone; MSH, melanocyte-stimulating hormone;
PC, prohormone-converting enzyme; POMC, proopiomelanocortin; JP, joining peptid
e.
65FF14.jpg|Fig. 65.14 Melanocortin-1 receptor within the plasma m
embrane of a melanocyte. The red dots represent alterations in the amino aci
d sequence (variants) compared with the wild type. Some of the variants are due
to loss-of-function mutations, i.e. the expected increase in intracellular cAMP
is not observed following the binding of MSH, whereas others have no effect on f
unction or lead to decreased function. Loss-of-function variants, e.g. Arg151Cys
, Arg160Trp, and Asp294His, have been associated with red hair. The tan dots rep
resent synonymous variants where there is no change in amino-acid sequence.
65FF15.jpg|Fig. 65.15 Activation of a G-protein-coupled receptor
such as the melanocortin-1 receptor (MC1-R). In the case of the MC1-R, the i
ncrease in the intracellular concentration of cAMP leads to an increase in tyros
inase activity and eumelanin production. GDP, guanosine diphosphate; GTP, guanos
ine triphosphate; P, phosphate group; S, stimulatory. Adapted from Alberts2
9.
65FF16.jpg|Fig. 65.16 Interaction of melanocyte-stimulating hormo
ne (MSH) and agouti signaling protein (ASP) with the melanocortin-1 receptor (MC
1-R). There is baseline activity of the MC1-R, enhanced by binding with MSH.
In mice, ASP represents an antagonist ligand for the MC1-R. Dysfunction of the
MC1-R can also lead to pheomelanogenesis, as in the case of humans with red hair
.
65FF17.jpg|Fig. 65.17 Alternating eumelanin and pheomelanin produ
ction in a fox hair. This pattern is referred to as agouti.
65FF18.jpg|Fig. 65.18 cAMP cascade. Patients with the McCune&
#8211;Albright syndrome (polyostotic fibrous dysplasia) are mosaics for an activ
ating mutation in the gene that encodes the G protein Gsα. As a
result, the cAMP cascade is permanently ‘turned on’.
65FT1.jpg|Table 65.1 Disorders characterized by diffuse pigmentar
y dilution in which the genetic defect is known. LYST, lysosomal trafficking
regulator gene; TRP, tyrosinase-related protein. *In Africa, brown a
lbinism has been linked to the P gene. †In mice, there are 15 i
nherited models of Hermansky–Pudlak syndrome; additional genes may be disc
overed in humans with the condition.
65FT2.jpg|Table 65.2 Variation of types of melanosome within mela
nocytes and keratinocytes with level of cutaneous pigmentation.
65FT3.jpg|Table 65.3 Differences between melanosomes in lightly p
igmented and darkly pigmented skin. Courtesy of Raymond Boiss, PhD.
65FT4.jpg|Table 65.4 Major forms of melanocortin receptor (MCR). ACTH, adrenocorticotropic hormone; APC, antigen-presenting cells; EC, endoth
elial cells; MSH, melanocyte-stimulating hormone. *Antagonistic ligan
ds – agouti protein (mouse) and agouti signaling protein (human). &#8
224;Antagonistic ligands – neuropeptide agouti-related protein.
66FF1.jpg|Fig. 66.1 Vitiligo. Complete loss of pigment of the
glans penis. Note the lack of any secondary changes. Courtesy of Jean Bolognia,
M.D.
66FF2.jpg|Fig. 66.2 Vitiligo. Depigmentation of the volar wri
sts as well as the palmar surfaces. Courtesy of Jean Bolognia, M.D.
66FF3.jpg|Fig. 66.3 Distribution of amelanotic skin lesions in vi
tiligo. Adapted with permission from Le Poole C, Boissy RE. Vitiligo. Semin
Cutan Med Surg. 1997;16:3–14.

66FF4.jpg|Fig. 66.4 Segmental vitiligo. Under normal light, v
itiligo can be subtle in lightly pigmented individuals. The clue to the diagnosi
s is the poliosis of the eyelashes. Courtesy of Jean Bolognia, M.D.
66FF5.jpg|Fig. 66.5 Inflammatory vitiligo. There is a figurat
e outline to the inflammatory border.
66FF6.jpg|Fig. 66.6 Segmental vitiligo. Unilateral band of de
pigmentation on the face, the most common location for segmental vitiligo. Note
the pigmented hairs within the affected area. Courtesy of Kalman Watsky, M.D.
66FF7.jpg|Fig. 66.7 Vitiligo of the elbow responding to PUVA ther
apy with a pattern of perifollicular repigmentation. The areas of repigmenta
tion are darker in color than the uninvolved skin. Courtesy of Jean Bolognia, M.
D.
66FF8.jpg|Fig. 66.8 Oculocutaneous albinism type 2 (OCA2). Af
rican patient with obvious squamous cell carcinoma on the cheek as well as multi
ple pigmented lentigines. Courtesy of James Nordlund, M.D.
66FF9.jpg|Fig. 66.9 African patient with hypopigmented hair, gray
irides, and large pigmented lentigines. Courtesy of James Nordlund, M.D.
66FF10.jpg|Fig. 66.10 Differential diagnosis of diffuse pigmentar
y dilution with onset at birth or during infancy. (Adapted with permission f
rom Blackwell Science Ltd.)
66FF11.jpg|Fig. 66.11 Piebaldism. White forelock and characte
ristic triangular amelanotic patch on the mid-forehead. Note the normally pigmen
ted macules of varying sizes within the leukoderma. Courtesy of Diane Davidson,
M.D.
66FF12.jpg|Fig. 66.12 Piebaldism. Mother and son with the cha
racteristic involvement of the mid-extremities. Note the normally pigmented macu
les within the leukoderma. Courtesy of Jean Bolognia, M.D.
66FF13.jpg|Fig. 66.13 Waardenburg's syndrome type 2. Heteroch
romia irides in the absence of dystopia canthorum. The white forelock is seen in
the upper left corner. Courtesy of Daniel Albert, M.D.
66FF14.jpg|Fig. 66.14 Movement of melanosomes into dendrites.
66FF15.jpg|Fig. 66.15 Tuberous sclerosis. Two types of hypome
lanotic macules – lanceovate and confetti (IGH-like). Courtesy of Dr Strob
el.
66FF16.jpg|Fig. 66.16 Hypomelanosis of Ito. Note the S-shaped
pattern of the hypopigmented streaks on the flank and abdomen because the lesio
ns are following Blaschko's lines.
66FF17.jpg|Fig. 66.17 Nevus depigmentosus. Hypomelanotic patc
h with decrease, but not absence, of pigmentation. Courtesy of Yale Residents Sl
ide Collection.
66FF18.jpg|Fig. 66.18 Differential diagnosis of linear leukoderma
.
66FF19.jpg|Fig. 66.19 Postinflammatory hypomelanosis. Hypopig
mentation secondary to psoriasis (A), seborrheic dermatitis in an infant
(B), pityriasis lichenoides chronic (C), and lichen striatus (D
). Note the flat-topped papules in the latter. Complete pigment loss in a pa
tient with severe atopic dermatitis (E) and discoid lupus erythematosus (
F). B, courtesy of Jean Bolognia, M.D.
66FF20.jpg|Fig. 66.20 Leukoderma of scleroderma. Uniform rete
ntion of perifollicular pigment within areas of leukoderma. Hyperpigmentation is
also seen overlying a superficial vein. Courtesy of Yale Residents Slide Collec
tion.
66FF21.jpg|Fig. 66.21 Guttate lichen sclerosus involving the areo
la. Courtesy of Yale Residents Slide Collection.
66FF22.jpg|Fig. 66.22 Pityriasis (tinea) versicolor. Hypopigm
ented variant with obvious scale. Courtesy of Yale Residents Slide Collection.
66FF23.jpg|Fig. 66.23 Tuberculoid leprosy. Large thin hypopig
mented plaque on the elbow with a raised pink border. Courtesy of Yale Residents
Slide Collection.
66FF24.jpg|Fig. 66.24 Onchocerciasis. Depigmentation of the s

hin with follicular repigmentation or retention of perifollicular pigment, a com
mon site for the associated leukoderma.
66FF25.jpg|Fig. 66.25 Melanoma-associated leukoderma. In a pa
tient with stage IV melanoma, amelanotic, vitiligo-like patches developed at mul
tiple sites including this excision site. Courtesy of Jean Bolognia, M.D.
66FF26.jpg|Fig. 66.26 Hypopigmentation due to injection of cortic
osteroids into the wrist joint. The outline is both stellate and linear. Cou
rtesy of Yale Residents Slide Collection.
66FF27.jpg|Fig. 66.27 Chemical leukoderma. Depigmentation dev
eloped at sites of contact with rubber swimming goggles. Courtesy of Kalman Wats
ky, M.D.
66FF28.jpg|Fig. 66.28 Idiopathic guttate hypomelanosis. A Typ
ical 1–5 mm macules on the shin. B Occasionally there is admix
ture of larger lesions. Courtesy of Yale Residents' slide collection.
66FF29.jpg|Fig. 66.29 Disseminated hypopigmented keratoses. O
ver 200 guttate minimally elevated hypopigmented papules developed after several
months of PUVA therapy. Histologically, there was no evidence of verruca plana.
Courtesy of Jean Bolognia, M.D.
66FT1.jpg|Table 66.1 Classification of oculocutaneous and ocular
albinism. OA, ocular albinism; OCA, oculocutaneous albinism; TYRP1, t
yrosinase related protein-1 gene; TYR, tyrosinase gene; MATP, memb
rane-associated transporter protein gene.
66FT2.jpg|Table 66.2 Differential diagnosis of scalp poliosis.
66FT3.jpg|Table 66.3 Disorders of melanocyte development. AD,
autosomal dominant; AR, autosomal recessive.
66FT4.jpg|Table 66.4 Disorders of melanosome transport and transf
er.
66FT5.jpg|Table 66.5 Differential diagnosis of guttate leukoderma
.
66FT6.jpg|Table 66.6 Disorders with linear lesions of hypopigment
ation.
66FT7.jpg|Table 66.7 Selected chemicals associated with chemical
leukoderma. Depigmentation weak or not known. Data from Gellin and Maibach (
1985), Ortonne et al. (1983)15, Taylor et al. (1993) and Miyamoto and
Taylor (2000).
66FT8.jpg|Table 66.8 Entities with premature graying of scalp hai
r.
66FT9.jpg|Table 66.9 Diffuse hypomelanosis of scalp hair. The
se are in addition to entities in Fig. 66.10.
67FF1.jpg|Fig. 67.1 Melasma (malar pattern). Hyperpigmentatio
n in an irregular pattern seen in an Hispanic woman.
67FF2.jpg|Fig. 67.2 Ashy dermatosis. Multiple gray-brown macu
les and patches on the thighs of a 10-year-old girl. This patient had involvemen
t of her trunk and upper extremities.
67FF3.jpg|Fig. 67.3 Ochronosis-like pigmentation on the face.
This rarely occurs after hydroquinone use.
67FF4.jpg|Fig. 67.4 Minocycline-induced pigmentation of the shin.
 Note the gray-blue color.
67FF5.jpg|Fig. 67.5 Approach to the adult patient with diffuse hy
perpigmentation. See the section on drug-induced hyperpigmentation for a com
plete list of drugs and chemicals.
67FF6.jpg|Fig. 67.6 Pigmentary demarcation lines (PDL). A The
most common PDL is on the upper arm with relative hypopigmentation on the ventr
al surface. B Type C PDL (composed of parallel lines) may be confused wit
h an achromic nevus. Courtesy Jean Bolognia, M.D.
67FF7.jpg|Fig. 67.7 Pigmentary demarcation lines.
67FF8.jpg|Fig. 67.8 Linear epidermal hyperpigmentation due to phy
tophotodermatitis. The desquamation is at site of previous bullae.
67FF9.jpg|Fig. 67.9 Linear postinflammatory hyperpigmentation. This pattern of hyperpigmentation presented on the forehead of an adolescent g
irl was due to excoriations.
67FF10.jpg|Fig. 67.10 Flagellate pigmentation. This young man
was prescribed bleomycin as a treatment for his lymphoma.
67FF11.jpg|Fig. 67.11 Linear and whorled nevoid hypermelanosis on
the trunk of a boy. He had no preceding lesions and no associated systemic
abnormalities. Note the distribution along the lines of Blaschko.
67FF12.jpg|Fig. 67.12 Approach to the patient with presumed linea
r and whorled nevoid hyperpigmentation.
67FF13.jpg|Fig. 67.13 Linear hyperpigmentation due to atrophoderm
a of Moulin. Note the subtle depression of the lesions on the upper lateral
thigh. Courtesy Jean Bolognia, M.D.
67FF14.jpg|Fig. 67.14 Histologic differences between stage III in
continentia pigmenti and linear and whorled nevoid hypermelanosis.
67FF15.jpg|Fig. 67.15 Stage III incontinentia pigmenti in a 2-yea
r-old infant. Note the characteristic gray-brown color, and the distribution
along the lines of Blaschko.
67FF16.jpg|Fig. 67.16 Confluent and reticulated papillomatosis of
Gougerot and Carteaud. A On the neck and back of a teenage girl (Courtesy o
f Dr Seth Orlow) and (B) on the chest of an older woman.
67FF17.jpg|Fig. 67.17 Erythema ab igne. Reticulated hyperpigm
entation on the lower back due to prolonged exposure to heat. Note the wide spac
ing of the net-like pattern.
67FF18.jpg|Fig. 67.18 Interaction between telomerase and dyskerin
. Telomerase, the enzyme that protects against progressive shortening of the
chromosomes which occurs with each successive cell division, is composed of two
subunits, hTR and hTERT. Dyskerin, the protein that is dysfunctional in patient
s with X-linked recessive DKC, interacts with telomerase and plays a role in its
proper function. RT, reverse transcriptase.
67FF19.jpg|Fig. 67.19 Dyskeratosis congenita. Reticulated hyp
erpigmentation on the chest and neck of a teenage boy. Courtesy of Seth Orlow, M
.D.
67FF20.jpg|Fig. 67.20 Dyschromatosis symmetrica hereditaria.
An admixing of multiple hypo- and hyperpigmented macules on the hands more so th
an the forearms. Courtesy Peter Ehrnstrom, M.D.
67FF21.jpg|Fig. 67.21 Dyschromatosis universalis hereditaria.
Both hypo- and hyperpigmentation were present in a widespread distribution. Wit
h permission from Urabe and Hori59.
67FT1.jpg|Table 67.1 Melasma differential diagnosis.
67FT2.jpg|Table 67.2 Drugs and chemicals associated with hyperpig
mentation. Modified from Kang et al, 199335.
67FT3.jpg|Table 67.3 Disorders associated with multiple lentigin
es. ECG, electrocardiogram; GI, gastrointestinal; LEOPARD, lentigines
/ECG abnormalities/ocular hypertelorism/pulmonary stenosis/
abnormalities of genitalia/retardation of growth/deafness s
yndrome; NAME, nevi/atrial myxoma/myxoid neurofibroma/ephelides syndrome; LAMB, lentigines/atrial myxoma/mucocu
taneous myxoma/blue nevi syndrome. *To date, observed in a single family;
#may fade; +persists. Modified from Bolognia, 200036
.
67FT4.jpg|Table 67.4 Disorders associated with multiple café
-au-lait macules. CNS, central nervous system. Modified from Bolognia, 200036.
67FT5.jpg|Table 67.5 Five major forms of pigmentary demarcation l
ines.
67FT6.jpg|Table 67.6 Disorders associated with postinflammatory h
yperpigmentation. Modified from Bolognia J, 200027.
67FT7.jpg|Table 67.7 Disorders with hyperpigmentation that can fo
llow Blaschko’s lines43. *Female patients; 
+Most have block-like configuration; ‡Single case.

67FT8.jpg|Table 67.8 Disorders characterized by reticulated pigme
ntation.
67FT9.jpg|Table 67.9 Dyschromatoses: hypo- and hyperpigmentation.

68FF1.jpg|Fig. 68.1 Hair and nail as products of epithelial redup
lication. Adapted from Chuong CM. Morphogenesis of epithelial appendages: va
riations on top of a common theme and implications in regeneration. In: Chuong C
M (ed.) Molecular Basis of Epithelial Appendage Morphogenesis. Austin: RG Landes
, 1998;3–14.
68FF2.jpg|Fig. 68.2 Hair follicle development and cycling.
68FF3.jpg|Fig. 68.3 Terminal human hair follicle in anagen VI. A Overview. B Proximal hair follicle.
68FF4.jpg|Fig. 68.4 Keratinocyte lineages in the hair follicle. From Taylor G, Lehrer MS, Jensen PJ, et al. Involvement of follicular stem ce
lls in forming not only the follicle but also the epidermis. Cell 2000;102:451&#
8211;61.
68FF5.jpg|Fig. 68.5 Schematic presentation of the onset of expres
sion of special keratins in the hair bulb. From Langbein L, Rogers MA, Praet
zel S, et al. A novel epithelial keratin, hK6irs, is expressed differentially in
all layers of the inner root sheath, including specialized Huxley cells (Fl&#25
2;gelzellen) of the human hair follicle. J Invest Dermatol. 2002;118:789–9
9.
68FF6.jpg|Fig. 68.6 Hair shaft structure.
68FF7.jpg|Fig. 68.7 Fetal development of the hair follicle.
68FF8.jpg|Fig. 68.8 Perifollicular innervation of murine back ski
n hair follicles. From Paus R, Peters EM, Eichmüller S, Botchkarev VA.
Neural mechanisms of hair growth control. J Invest Dermatol Symp Proc. 1997;2:61
–8.
68FF9.jpg|Fig. 68.9 Key signaling events in murine hair follicle
development. Modified from Millar SE. Molecular mechanisms regulating hair f
ollicle development. J Invest Dermatol. 2002;118:216–25.
68FF10.jpg|Fig. 68.10 Hair cycle control.
68FF11.jpg|Fig. 68.11 Switches in the local signaling milieu driv
e hair follicle cycling. From Paus R, Böttge JA, Henz BM, Maurer M. Hai
r growth control by immunosuppression. Arch Dermatol Res. 1996;288:408–10.
68FF12.jpg|Fig. 68.12 Interactions between DP fibroblasts and epi
thelial hair follicle stem cells during anagen induction. A Bulge activation
hypothesis. B Hypothesis of hair follicle predetermination. A, from Cots
arelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of p
ilosebaceous unit: implications for follicular stem cells, hair cycle, and skin
carcinogenesis. Cell. 1990;61:1329–37; B, from Panteleyev AA, Jahoda CAB,
Christiano AM. Hair follicle predetermination. J Cell Sci. 2001;114:3419–3
1.
68FF13.jpg|Fig. 68.13 Proposed histodynamics of anagen hair folli
cle construction. Adapted from Panteleyev AA, Jahoda CAB, Christiano AM. Hai
r follicle predetermination. J Cell Sci. 2001;114:3419–31.
68FF14.jpg|Fig. 68.14 Embryological development of the nail appar
atus.
68FF15.jpg|Fig. 68.15 Anatomical structure of the nail apparatus.

68FF16.jpg|Fig. 68.16 Distribution of keratins and non-keratin pr
oteins in the nail apparatus. Adapted from Dawber RPR, de Berker DAR, Baran
R. Science of the nail apparatus. In: Baran R, Dawber RPR, de Berker DAR, et al
(eds) Diseases of the Nails and their Management. Oxford: Blackwell Science, 200
1;1–47.
68FF17.jpg|Fig. 68.17 Theories on the origin of the nail plate. Adapted from Dawber RPR, de Berker DAR, Baran R. Science of the nail apparatu
s. In: Baran R, Dawber RPR, de Berker DAR, et al (eds) Diseases of the Nails and
their Management. Oxford: Blackwell Science, 2001;1–47.
68FT1.jpg|Table 68.1 Complex functions of hair and nails.

68FT2.jpg|Table 68.2 Basic data of human hair follicles.
68FT3.jpg|Table 68.3 Trichology terms.
68FT4.jpg|Table 68.4 Human nail apparatus – basic data.
68FT5.jpg|Table 68.5 Ultrastructural differences of the onychocyt
es in distinct layers of the nail plate.
68FT6.jpg|Table 68.6 Factors that can influence nail growth.
69FF1.jpg|Fig. 69.1 Normal human scalp anagen hair follicle.
Montage of four Z-series, each collected with laser scanning confocal microscopy
. Red: fluorescein-conjugated lectin Ulex europaeus agglutinin (UEA1-FITC
) which stains blood vessels, follicular keratinocytes, and a subset of epiderma
l keratinocytes. Green: protein gene product 9.5 (PGP 9.5) antibody staining ner
ves. Highlighted are the subepidermal nerve plexus, arrector pili muscle, sweat
glands and perifollicular nerves.
69FF2.jpg|Fig. 69.2 Laser scanning confocal microscopic picture o
f the middle part of the dermal papilla. Presented is fluorescein-conjugated
lectin Ulex europaeus agglutinin (UEA1-FITC) staining of the vasculature
and follicular keratinocytes in and around the dermal papilla of the normal hum
an scalp anagen hair follicle.
69FF3.jpg|Fig. 69.3 Confocal laser scanning microscopic picture o
f the bulge region of the normal human hair follicle. Red: conjugated-conjug
ated lectin Ulex europaeus agglutinin (UEA1-FITC) of the vasculature in t
he bulge region. Green: protein gene product (PGP 9.5) staining of perifollicula
r nerves and the innervation of the arrector pili muscle.
69FF4.jpg|Fig. 69.4 The bulge activation hypothesis. ORS, out
er root sheath; IRS, inner root; S, sebaceous gland sheath; B, bulge; APM, arrec
tor pili muscle; DP, dermal papilla.
69FF5.jpg|Fig. 69.5 Materials needed for examination of hair fibe
rs.
69FF6.jpg|Fig. 69.6 Microscopic examination of hair fiber ‘
roots’. A Telogen fibers showing a club shape. B Anagen fibers
with attached inner root sheath, demonstrating pigmented, distorted bulbs appear
ing like the end of a broom stick.
69FF7.jpg|Fig. 69.7 Skin explant experiments in alopecia areata. Only transfer of T cells cultured with a follicular homogenate resulted in h
air loss.
69FF8.jpg|Fig. 69.8 Clinical features of alopecia areata. A P
atchy focal scalp alopecia areata. B Ophiasis pattern alopecia areata. C Diffuse variant. D Extensive alopecia areata (alopecia totalis).
69FF9.jpg|Fig. 69.9 Vertical section of a scalp biopsy specimen. An anagen follicle/hair bulb is surrounded by a primarily lymphocytic infilt
rate in the peribulbar region and external root sheath.
69FF10.jpg|Fig. 69.10 Alopecia areata. A Horizontal section o
f a normal human scalp biopsy stained with hematoxylin and eosin. Follicular uni
ts are depicted, each consisting of primarily two to four anagen follicles. Mini
mal inflammation is noted. B Horizontal section of a scalp biopsy stained with h
ematoxylin and eosin. The specimen was taken from a patient with extensive alope
cia areata (>90%) of ten years duration. Note the miniaturized follicles wit
hin follicular units and that a perifollicular inflammatory process is still app
arent even after a decade of extensive, chronic scalp hair loss.
69FF11.jpg|Fig. 69.11 Lichen planopilaris affecting the scalp. Note the perifollicular erythema at the periphery area of alopecia.
69FF12.jpg|Fig. 69.12 Frontal fibrosing alopecia.
69FF13.jpg|Fig. 69.13 Classic pseudopelade. Note the discrete
, smooth, skin-colored areas of alopecia without follicular hyperkeratosis or pe
rifollicular inflammation.
69FF14.jpg|Fig. 69.14 Folliculitis necrotica.
69FF15.jpg|Fig. 69.15 Examination of a normal hair fiber with pol
arizing microscopy. The medulla is blue, the cortex is pink-red and the cuti
cle is yellow.
69FF16.jpg|Fig. 69.16 Trichorrhexis invaginata (bamboo hair).

69FF17.jpg|Fig. 69.17 Monilethrix. A Ultrastructure showing a
lternating elliptical nodes and constrictions and B clinical presentation
of monilethrix.
69FF18.jpg|Fig. 69.18 Trichorrhexis nodosa.
69FF19.jpg|Fig. 69.19 Woolly hair nevus.
69FF20.jpg|Fig. 69.20 5α-Reductase isozyme activity in adult
human tissues. Type I 5α-reductase is predominantly present in sebaceo
us glands and in the liver as well as in scalp hair follicles, whereas type II 5
-α-reductase is present in scalp beard and chest hair follicles, liver and
the prostate gland.
69FF21.jpg|Fig. 69.21 Localization of androgen-metabolizing enzym
es in the normal hair follicle. Using a variety of techniques, investigators
have localized these enzymes to various regions of the hair follicle. HSD, hydr
oxysteroid dehydrogenase.
69FF22.jpg|Fig. 69.22 Classification of male pattern baldness. A Hamilton's classification and B Norwood's classification.
69FF23.jpg|Fig. 69.23 Mechanism of action for antiandrogens and f
inasteride. Finasteride is a competitive inhibitor of type II 5α-reduct
ase, while antiandrogens block the interaction of testosterone with its receptor
. T, testosterone; DHT, dihydrotestosterone; 5αR, 5α-reductase; AR, an
drogen receptor.
69FF24.jpg|Fig. 69.24 Ludwig patterns of hair loss in women.
69FF25.jpg|Fig. 69.25 Trichotillomania. Note the well defined
area of triangular alopecia.
69FT1.jpg|Table 69.1 Subtypes of telogen effluvium hair loss.
69FT2.jpg|Table 69.2 Treatment options for the management of alop
ecia areata.
69FT3.jpg|Table 69.3 Proposed working classification of primary c
icatricial alopecia.
69FT4.jpg|Table 69.4 The 2001 Workshop on Cicatricial Alopecias. Summary of hypotheses to be tested, confirmed or excluded29
69FT5.jpg|Table 69.5 Classification of hair structural abnormalit
ies.
69FT6.jpg|Table 69.6 Classification of female pattern hair loss.
69FT7.jpg|Table 69.7 DSM-IV diagnostic criteria for trichotilloma
nia.
70FF1.jpg|Fig. 70.1 Hypertrichosis in association with a Becker's
nevus. Courtesy of Jean Bolognia, M.D.
70FF2.jpg|Fig. 70.2 Nevoid hypertrichosis of the scalp in a young
boy. There was no underlying melanocytic nevus or hyperpigmentation. Courte
sy of Jean Bolognia, M.D.
70FF3.jpg|Fig. 70.3 Acquired localized hypertrichosis. This m
an worked a great deal on his knees laying tiles; the scar is due to a total kne
e replacement. Courtesy of Jean Bolognia, M.D.
70FF4.jpg|Fig. 70.4 Central hirsutism, score 3, in a woman adrena
l SAHA syndrome.
70FF5.jpg|Fig. 70.5 Familial hirsutism.
70FF6.jpg|Fig. 70.6 Glucocorticoids and androgens synthesis.
70FF7.jpg|Fig. 70.7 Hirsutism in Stein–Leventhal's syndrome
(score 3–4).
70FF8.jpg|Fig. 70.8 Facial hirsutism (score 4) due to ovarian hyp
erthecosis. Courtesy of Robert Hartman, M.D.
70FF9.jpg|Fig. 70.9 Degrees of hirsutism. Ferriman & Gall
wey score.
70FF10.jpg|Fig. 70.10 Differential diagnosis of hirsutism.
70FF11.jpg|Fig. 70.11 Adrenal SAHA syndrome. Before (A
) and after (B) laser treatment.
70FT1.jpg|Table 70.1 Hypertrichosis in congenital and hereditary
diseases.
70FT2.jpg|Table 70.2 Hypertrichosis due to drugs.
70FT3.jpg|Table 70.3 Abraham’s classification of hirsutism.
 Based on the Ferriman and Gallwey score (see Fig. 70.9).
71FF1.jpg|Fig. 71.1 Schematic drawing of the nail apparatus in lo
ngitudinal section.
71FF2.jpg|Fig. 71.2 Nail signs.
71FF3.jpg|Fig. 71.3 Nail pitting due to psoriasis. Pits are l
arge, deep and irregularly scattered, in contrast with alopecia areata where the
y are small, superficial and geometrically distributed.
71FF4.jpg|Fig. 71.4 Trachyonychia (twenty nail dystrophy). Th
e nails seem sandpapered in a longitudinal direction.
71FF5.jpg|Fig. 71.5 Causes of onycholysis.
71FF6.jpg|Fig. 71.6 Longitudinal melanonychia. The longitudin
al melanonychia is due to a congenital melanocytic nevus of the nail matrix.
71FF7.jpg|Fig. 71.7 Darier's disease. Alternating longitudina
l red and white streaks with distal fissuring. Courtesy of Yale Residents Slide
Collection.
71FF8.jpg|Fig. 71.8 Nail psoriasis. The nails show salmon pat
ches and onycholysis with an erythematous border.
71FF9.jpg|Fig. 71.9 Hallopeau's acrodermatitis. Note the rela
psing pustular eruption of the nail bed and distal finger.
71FF10.jpg|Fig. 71.10 Nail lichen planus. Note the nail thinn
ing with longitudinal ridging and fissuring.
71FF11.jpg|Fig. 71.11 Yellow nail syndrome. Courtesy of Yale
71FF12.jpg|Fig. 71.12 Multiple periungual pyogenic granulomas in
a patient taking indinavir.
71FF13.jpg|Fig. 71.13 Median nail dystrophy due to habitual tic.
71FF14.jpg|Fig. 71.14 Myxoid cyst. The longitudinal nail groo
ve is a result of the proximal nail fold compression of the nail matrix.
71FF15.jpg|Fig. 71.15 Onychomatricoma. The nail is thickened
and overcurved with longitudinal yellow streaks. The distal border shows several
holes.
71FF16.jpg|Fig. 71.16 Bowen's disease. The lateral portion of
the nail plate is absent. The nail bed shows hyperkeratosis with scaling and fi
ssuring of the epithelium.
71FF17.jpg|Fig. 71.17 Amelanotic melanoma. Note the diffuse n
ail destruction and ulceration.
71FT1.jpg|Table 71.1 Correlation of nail findings with anatomical
site of nail damage.
71FT2.jpg|Table 71.2 Causes of longitudinal melanonychia.
71FT3.jpg|Table 71.3 Systemic conditions associated with clubbing
.
71FT4.jpg|Table 71.4 Drug-induced nail abnormalities.
72FF1.jpg|Fig. 72.1 Geographic tongue. This is a florid examp
le of geographic tongue, demonstrating well-delineated areas of erythema partial
ly surrounded by yellowish-white serpiginous borders.
72FF2.jpg|Fig. 72.2 Fissured tongue. Numerous asymptomatic fu
rrows and grooves characterize this condition.
72FF3.jpg|Fig. 72.3 Hairy tongue. The dorsum of the tongue ex
hibits marked accumulation of keratin and brown discoloration.
72FF4.jpg|Fig. 72.4 Aspirin burn. To relieve a toothache, thi
s patient placed an aspirin in the mouth adjacent to the symptomatic tooth. Note
the wrinkled white membrane that represents superficial epithelial necrosis.
72FF5.jpg|Fig. 72.5 Cheek chewing (morsicatio buccarum). Repe
titive nibbling of the superficial layers of the epithelium resulted in these ch
anges. Note that the characteristic shaggy, white lesion approximates the area w
here the upper and lower teeth meet.
72FF6.jpg|Fig. 72.6 Traumatic ulcer. This lesion of the later

al tongue demonstrates a yellow fibrinopurulent membrane with a white border of
hyperkeratosis. Compare this to the exophytic, ulcerated mass depicted in , whic
h represents oral SCC.
72FF7.jpg|Fig. 72.7 Contact stomatitis from artificial cinnamon f
lavoring. Use of artificial cinnamon-flavored gum caused this shaggy, white
hyperkeratotic lesion of the buccal mucosa.
72FF8.jpg|Fig. 72.8 Recurrent aphthous stomatitis. Shallow, c
reamy-white ulceration surrounded by an intensely red halo and located on non-ke
ratinized mucosa, representing the classic appearance of this lesion.
72FF9.jpg|Fig. 72.9 Cheilitis granulomatosa. Asymmetric swell
ing predominantly of the lower lip. The biopsy specimen showed non-necrotizing g
ranulomata.
72FF10.jpg|Fig. 72.10 Leukoplakia. Sharply demarcated, white
plaque involving the ventral surface of the tongue and floor of the mouth.
72FF11.jpg|Fig. 72.11 Nicotine stomatitis. Gray-white palatal
mucosa with numerous umbilicated papules representing inflamed palatal mucous g
lands.
72FF12.jpg|Fig. 72.12 Squamous cell carcinoma. Ulcerated, ind
urated, exophytic mass involving the right lateral border of the tongue, a typic
al presentation and site for this lesion.
72FF13.jpg|Fig. 72.13 Cheilitis glandularis. Erythematous muc
osal macules on the lower lip at sites of inflammed salivary gland ducts. There
is also evidence of actinic cheilitis.
72FF14.jpg|Fig. 72.14 Candidiasis/pernicious anemia. Erythema
tous, atrophic tongue as a manifestation of pernicious anemia with a superimpose
d candidal infection.
72FF15.jpg|Fig. 72.15 Crohn's disease. Linear ulceration of t
he mandibular vestibule: the classic oral manifestation of this disease.
72FF16.jpg|Fig. 72.16 Oral hairy leukoplakia. This shaggy whi
te hyperkeratotic lesion of the lateral tongue is caused by Epstein–Barr v
irus, and is most commonly seen in patients with HIV infection or other severely
immunosuppressed states.
72FT1.jpg|Table 72.1 The major clinical features of nevoid basal
cell carcinoma syndrome.
72FT2.jpg|Table 72.2 Multiple endocrine neoplasia (MEN) syndrome.

72FT3.jpg|Table 72.3 Oral manifestations of HIV-related condition
s48,49.
73FF1.jpg|Fig. 73.1 The normal vulva.
73FF2.jpg|Fig. 73.2 The normal penis.
73FF3.jpg|Fig. 73.3 The diagnosis of vulvar burning/pain in the s
etting of a normal appearing vulva.
73FF4.jpg|Fig. 73.4 The diagnosis of vulvar pruritus.
73FF5.jpg|Fig. 73.5 The diagnosis of anogenital pruritus.
73FF6.jpg|Fig. 73.6 Lichen sclerosus of the anus. Note the pa
llor.
73FF7.jpg|Fig. 73.7 Lichen sclerosus of the vulva with characteri
stic purpura. Courtesy of Kalman Watsky, MD.
73FF8.jpg|Fig. 73.8 Lichen sclerosus of the vulva. There is m
arked architectural change with loss of the labia minora and marked midline fusi
on.
73FF9.jpg|Fig. 73.9 Lichen sclerosus of the penis. Erythemato
us and white plaque on the glans. Courtesy of Ron Rapini, MD.
73FF10.jpg|Fig. 73.10 Lichen planus. An annular band is seen
on the shaft of the penis. This is a typical finding.
73FF11.jpg|Fig. 73.11 Erosive lichen planus of the vulva. Int
roital erosions are surrounded by a lacy white border with severe scarring.
73FF12.jpg|Fig. 73.12 Plasma cell balanitis. There are moist
‘kissing lesions’ on adjacent surfaces of the glans and prepuce.
73FF13.jpg|Fig. 73.13 Vulvar dermatitis. Lichenification is p

rominent. The underlying diagnosis was atopic dermatitis.
73FF14.jpg|Fig. 73.14 Penile intraepithelial neoplasia. Persi
stent erythema not responding to topical steroids.
73FF15.jpg|Fig. 73.15 Squamous cell carcinoma of the foreskin. This patient with psoriasis had received PUVA therapy without genital protecti
on.
73FF16.jpg|Fig. 73.16 Extramammary Paget' s disease of the perian
al area. Note the well-demarcated erythema. There is a ‘strawberries a
nd cream’ appearance.
73FF17.jpg|Fig. 73.17 Cicatricial pemphigoid of the vulva. A
There is marked scarring of the vulva (positive direct immunofluorescence distin
guished this from erosive lichen planus). B The same patient has typical
gingival erythema.
73FT1.jpg|Table 73.1 Therapies for anogenital lichen sclerosus
73FT2.jpg|Table 73.2 Causes of vulvar pain.
73FT3.jpg|Table 73.3 Benign lesions of the genitalia (from most t
o least common).
73FT4.jpg|Table 73.4 Causes of genital erosions.
74FF1.jpg|Fig. 74.1 Bullous impetigo. Superficial bullae and
dry erosion of the nose due to infection with Staphylococcus aureus. Cour
74FF2.jpg|Fig. 74.2 Ecthyma. Ulceration with hemorrhagic crus
t on the wrist due to infection with group A streptococci. Courtesy of Kalman Wa
tsky M.D.
74FF3.jpg|Fig. 74.3 Interaction of bacterial superantigen with ma
jor histocompatibility complex and T-cell receptors.
74FF4.jpg|Fig. 74.4 Hyperemia of the conjunctiva in a patient wit
h toxic shock syndrome due to S. aureus infection. Courtesy of Yale R
74FF5.jpg|Fig. 74.5 Erysipelas. Well-demarcated erythema of t
he face. Courtesy of Yale Residents Slide Collection.
74FF6.jpg|Fig. 74.6 Extensive cellulitis of the lower extremity w
ith the formation of bullae secondary to group A streptococcal infection. Co
urtesy of Yale Residents Slide Collection.
74FF7.jpg|Fig. 74.7 Approach to the patient with cellulitis.
74FF8.jpg|Fig. 74.8 Necrotizing fasciitis. Necrosis of the subcut
aneous fat and fascia of the inner aspect of the upper arm in an elderly patient
with diabetes mellitus. Note the watery discharge.
74FF9.jpg|Fig. 74.9 Erythrasma. Large brown patch in the axil
la (A) and coral-red fluorescence with Wood's lamp illumination (B
).
74FF10.jpg|Fig. 74.10 Pitted keratolysis of the plantar surface o
f the foot. Multiple small craters with decreased stratum corneum. Courtesy
of Kalman Watsky M.D.
74FF11.jpg|Fig. 74.11 Trichomycosis axillaris. Cylindrical sh
eaths and beading of the axillary hairs. Courtesy of Yale Residents Slide Collec
tion.
74FF12.jpg|Fig. 74.12 Acute meningococcemia. Large areas of p
urpura with central gunmetal-gray discoloration.
74FF13.jpg|Fig. 74.13 Chronic meningococcemia. Multiple eryth
ematous crusted papules and nodules on the arm. Courtesy of Yale Residents Slide
Collection.
74FF14.jpg|Fig. 74.14 Superficial infection of the skin with P
seudomonas. Note the macerated border, the erosions and the moth-eaten a
ppearance of the skin. Courtesy of Kalman Watsky M.D.
74FF15.jpg|Fig. 74.15 Ecthyma gangrenosum. Embolic lesion of
Pseudomonas aeruginosa on the chest. Note the necrotic center and inflamm
atory border.
74FF16.jpg|Fig. 74.16 Clinical manifestations of brucellosis.

With permission from Slack MPE. Gram-negative coccobacilli. In: Armstrong D, Co
hen J (eds). Infectious Diseases. London: Mosby, 1999.
74FF17.jpg|Fig. 74.17 Clinical types of tularemia. Adapted wi
th permission from Slack MPE. Gram-negative coccobacilli. In: Armstrong D, Cohen
J (eds). Infectious Diseases. London: Mosby, 1999.
74FF18.jpg|Fig. 74.18 Transmission cycles of Yersinia pestis. With permission from Dennis DT, Gage KL. Plague. In: Armstrong D, Cohen
J (eds). Infectious Diseases. London: Mosby, 1999.
74FF19.jpg|Fig. 74.19 Hemorrhagic bullae of the leg secondary to
Vibrio vulnificus infection.
74FF20.jpg|Fig. 74.20 Expanding erythematous plaque of erythema m
igrans on the neck.
74FF21.jpg|Fig. 74.21 The acral skin is atrophic and shiny, with
prominent superficial veins in this patient with acrodermatitis chronica atrophi
cans. Courtesy of Yale Residents Slide Collection.
74FF22.jpg|Fig. 74.22 Cutaneous yaws on the knee of an adolescent
from Indonesia. Courtesy of Peter Ehrnstrom M.D.
74FF23.jpg|Fig. 74.23 Cervicofacial actinomycosis or ‘lumpy
jaw’ with soft tissue swelling and draining ulcerated nodules. The di
scharge contained sulfur granules. Courtesy of Peter Ehrnstrom M.D.
74FT1.jpg|Table 74.1 Normal skin flora.
74FT2.jpg|Table 74.2 Differential diagnosis of non-bullous and bu
llous impetigo.
74FT3.jpg|Table 74.3 Comparison between toxic epidermal necrolysi
s (TEN) and staphylococcal scalded skin syndrome (SSSS).
74FT4.jpg|Table 74.4 Case definitions for the toxic shock syndrom
es.
74FT5.jpg|Table 74.5 The toxic shock syndromes (staphylococcal ve
rsus streptococcal).
74FT6.jpg|Table 74.6 Comparison between clostridial anaerobic cel
lulitis and clostridial myonecrosis.
74FT7.jpg|Table 74.7 Skin eruptions associated with ehrlichiosis.

74FT8.jpg|Table 74.8 Major extracutaneous features of Lyme diseas
e.
75FF1.jpg|Fig. 75.1 Worldwide distribution of leprosy. Reprod
uced from WHO11
75FF2.jpg|Fig. 75.2 The clinical–immunologic spectrum of le
prosy. This reflects the underlying host immunity as measured by the T-lymph
ocyte and antibody responses to Mycobacterium leprae. Spontaneous fluctua
tions in the immune response are responsible for type 1 and type 2 reactions. TT
, tuberculoid leprosy; BT, borderline–tuberculoid leprosy; BB, mid-borderl
ine leprosy; BL, borderline–lepromatous leprosy; LL, lepromatous leprosy;
IFN, interferon; IL, interleukin. Modified from Britton WJ. Leprosy. In Armstron
g D, Cohen J, Infectious Diseases. London: Mosby, 1999.
75FF3.jpg|Fig. 75.3 Nerve examination sites.
75FF4.jpg|Fig. 75.4 Lepromatous leprosy. Note the diffuse inf
iltration of the face with leonine facies and madarosis.
75FF5.jpg|Fig. 75.5 Sequelae of leprosy.
75FF6.jpg|Fig. 75.6 Sequele of leprosy. The patient has madur
osis, a saddle nose and blindness in the left eye. Courtesy of Evangeline Handog
, M.D.
75FF7.jpg|Fig. 75.7 Borderline lepromatous leprosy. Multiple
erythemous plaques are seen, some with central clearing.
75FF8.jpg|Fig. 75.8 Tuberculoid leprosy. Note the elevated bo
rder and central hypopigmentation. Courtesy of Robert Hartman, M.D.
75FF9.jpg|Fig. 75.9 Leprosy reactions. Type 1 ‘upgradin
g’ reaction in a patient with borderline lepromatous disease characterized
by marked inflammation of a facial plaque (A). Erythema nodosum leprosum
(type 2 reaction) with the appearance of multiple red papulonodules in a patien

t with lepromatous leprosy (B).
75FF10.jpg|Fig. 75.10 Lepromatous leprosy. Diffuse infiltrate
of foamy histiocytes (macrophages) in the dermis, separated from the epidermis
by a Grenz zone. Courtesy of Ron Rapini, M.D.
75FF11.jpg|Fig. 75.11 Tuberculoid leprosy. A Linear granuloma
following the course of a nerve. B Higher power view of granuloma surrou
nding the nerve. Courtesy of Ron Rapini, M.D.
75FF12.jpg|Fig. 75.12 Map of tuberculosis notification rates worl
dwide. Reproduced from WHO37 .
75FF13.jpg|Fig. 75.13 Scrofuloderma. Note the retraction surr
ounding the deep ulcerations.
75FF14.jpg|Fig. 75.14 Orificial tuberculosis. A non-healing u
lcer at the tip of the tongue
75FF15.jpg|Fig. 75.15 Lupus vulgaris.
75FF16.jpg|Fig. 75.16 Papulonecrotic tuberculid. Erythematous
papules and papulopustules on the heel. Courtesy of Yale Residents Slide Collec
tion.
75FF17.jpg|Fig. 75.17 Enlarging granulomatous plaque at the site
of a BCG vaccination. Courtesy of Yale Residents Slide Collection.
75FF18.jpg|Fig. 75.18 Targets of the antituberculosis agents.
Modified from Grange JM, Alimuddin Z. Antituberculous agents. In Armstrong D, C
ohen J, Infectious Diseases. London: Mosby, 1999.
75FF19.jpg|Fig. 75.19 Mycobacterium marinum infections. A range of presentations including a bluish-red nodule with scale-crust at the
inoculation site on the lateral hand (A), a sporotrichoid pattern with t
he inoculation site on the distal third finger (B), and disseminated necr
otic lesions on the face of an immunocompromised patient (C).
75FF20.jpg|Fig. 75.20 Lymphangitic spread by Mycobacter
ium fortuitum. The inoculation chancre was on the foot. Courtesy Rubem A
zulay, M.D52 .
75FF21.jpg|Fig. 75.21 Mycobacterium chelonei infection. This immunosuppressed patient presented with an area of warmth and erythema on
the ankle (A). Acid-fast bacilli (stain red) in a biopsy specimen (B).
75FT1.jpg|Table 75.1 Mycobacteria that cause cutaneous disease. Modified classification of Runyon1,3,5. aCapable of yel
low pigment formation upon exposure to light. bCapable of yellow pigm
ent production without light exposure. cIncapable of pigment producti
on.
75FT2.jpg|Table 75.2 Classification of leprosy. Modified from
the WHO A Guide to Leprosy22. LL, lepromatous leprosy; BL, borderlin
e LL; BB, mid borderline leprosy; BT, borderline-tuberculoid; TT, tuberculoid le
prosy; I, intermediate.
75FT3.jpg|Table 75.3 Two major types of leprosy reactions12,
18,20,25.
75FT4.jpg|Table 75.4 Multidrug therapy/WHO scheme for the treatme
nt of leprosy. These recommendations are those currently standardized by the
WHO.7,23,28,29,30 *WHO classification for endemic areas when no faci
lities for performing bacilloscopy are available. MB, multibacillary; PB, paucib
acillary.
75FT5.jpg|Table 75.5 Clinical presentations of cutaneous tubercul
osis.
75FT6.jpg|Table 75.6 Spectrum of activity, class of compound and
cross-resistances of the antituberculosis agents. Agents that are active aga
inst tubercle bacilli (M. tuberculosis complex) may also show activity ag
ainst some other species of mycobacteria. Strains of M. bovis are natural
ly resistant to pyrazinamide. There are only limited data on other activities of
capreomycin and viomycin. From Grange JM, Alimuddin Z. Antituberculosis agents.
In Armstrong D, Cohen J, Infectious Diseases. London: Mosby, 1999.
75FT7.jpg|Table 75.7 Initial treatment of tuberculosis. Modif

ied from Chesnutt & Prendergast3,39,41,42,43. R, rifampicin 10 mg
/kg daily; I, isoniazid 5 mg/kg daily; P, pyrazinamide 30 mg/kg daily; S, strept
omycin 15 mg/kg daily; E, ethambutol 15 mg/kg daily. * S or E may be discontinue
d if Mycobacterium is susceptible to R and I
75FT8.jpg|Table 75.8 Treatment of atypical mycobacteria44,45
,47–51.
76FF1.jpg|Fig. 76.1 Rocky Mountain spotted fever. Note the ma
culopapular eruption with central petechiae.
76FF2.jpg|Fig. 76.2 Rocky Mountain spotted fever. The eruptio
n spreads centipetally and becomes diffuse.
76FF3.jpg|Fig. 76.3 Pathology of Rocky Mountain spotted fever.
76FT1.jpg|Table 76.1 Principal spotted fevers and their associati
on with tick genera and rickettsial species1.
76FT2.jpg|Table 76.2 Etiology and epidemiology of spotted fever g
roup of rickettsial disease.
77FF1.jpg|Fig. 77.1 Causes of nodules on hair shafts.
77FF2.jpg|Fig. 77.2 Pityriasis (tinea) versicolor, hyperpigmented
variant. Courtesy of Kalman Watsky, M.D.
77FF3.jpg|Fig. 77.3 Potassium hydroxide preparations. A Super
ficial skin scrapings from pityriasis (tinea) versicolor demonstrating yeast and
short mycelial forms. B A dermatophyte, in this case T. tonsurans
, demonstrating branching hyphae. A, Courtesy of Ron Rapini, M.D.
77FF4.jpg|Fig. 77.4 The migration of T. rubrum.
T. rubrum was originally concentrated in west Africa and southeast Asia
with subsequent westward migration to western Europe, the US, and Central and So
uth America.
77FF5.jpg|Fig. 77.5 Tinea corporis. A Annular lesion on the a
rm with active scaly border. B Widespread involvement of the back with sc
alloped inferior border. C Pustules within multiple figurate lesions on t
he upper arm.
77FF6.jpg|Fig. 77.6 Majocchi's granuloma. Perifollicular infl
ammation and pustules on the buttocks due to T. rubrum.
77FF7.jpg|Fig. 77.7 Tinea cruris. Note the arciform erythemat
ous border on the upper inner thigh.
77FF8.jpg|Fig. 77.8 Tinea manuum. Diffuse scaling of the palm
s with accentuation in the creases. Courtesy of Kalman Watsky, M.D.
77FF9.jpg|Fig. 77.9 Tinea barbae. More superficial form due t
o T. rubrum. Several follicular pustules are seen. Courtesy of Jean Bolog
nia, M.D.
77FF10.jpg|Fig. 77.10 Tinea faciei. The clues to the diagnosi
s include the pustule on the right cheek and the scale within the active border
on the nose. Courtesy of Kalman Watsky, M.D.
77FF11.jpg|Fig. 77.11 Tinea capitis. The range of clinical pr
esentations of tinea capitis due to T. tonsurans, from mild scalp scaling
(A) to patchy alopecia with scale (B) to large areas of alopecia
with pustules and scale crust (C) to kerion formation (D). Microsc
opic examination of involved hairs demonstrates and endothrix pattern (KOH-chlor
azol black stain; E).
77FF12.jpg|Fig. 77.12 Microscopic representation of the three pat
terns of hair invasion.
77FF13.jpg|Fig. 77.13 Favus due to T. schoenleinii. Scarring alopecia with erosions and several scutula on the occipital scalp.
The latter represent masses of keratin plus fungi. Courtesy of Israel Dvoretzky
, M.D.
77FF14.jpg|Fig. 77.14 Tinea pedis. Interdigital maceration be
tween the third and fourth toes (A) and erythema, scale-crust and bullae
in the inflammatory form (B). A, Courtesy of Jean Bolognia, M.D.
77FF15.jpg|Fig. 77.15 Tinea unguium. Onycholysis, yellowing,
crumbling and thickening of the fingernails (A) and toenails (B).

Courtesy of Jean Bolognia, M.D.
77FF16.jpg|Fig. 77.16 Diagnostic algorithm for dystrophy of one o
r more nails. An organized approach is essential in correctly and efficientl
y diagnosing onychomycosis.
77FF17.jpg|Fig. 77.17 Proper specimen collection. Proper coll
ection of skin, hair and nails is important. Following these simple guidelines w
ill help the clinician to achieve the most accurate diagnosis. (Courtesy of Judy
Warner)
77FF18.jpg|Fig. 77.18 Microscopic appearance of various forms of
conidia and hyphae and the in vitro hair perforation test.
77FF19.jpg|Fig. 77.19 Cutaneous candidiasis. This infection o
ccurred in a hospitalized patient with diabetes mellitus who was receiving broad
spectrum antibiotics. Note the multiple satellite lesions.
77FF20.jpg|Fig. 77.20 Granuloma gluteale infantum. Multiple d
ark red papules and nodules in an infant. Courtesy of Robert Hartman, M.D.
77FF21.jpg|Fig. 77.21 Chromomycosis. Annular and figurate pla
ques due to central clearing and scarring with a verrucous surface on the arm (A) and a more granulomatous appearance on the leg (B).
77FF22.jpg|Fig. 77.22 Madura foot. Note the soft tissue swell
ing of the foot as well as multiple nodules with pustular discharge.
77FF23.jpg|Fig. 77.23 Sporotrichosis. The primary lesion is o
n the third finger with multiple papules and nodules along the lymphatics of the
hand and forearm.
77FF24.jpg|Fig. 77.24 Histoplasmosis. Disseminated crusted an
d papulosquamous lesions in a patient with AIDS.
77FF25.jpg|Fig. 77.25 Blastomycosis. Well-demarcated plaques
with erosions, central scarring and black crusting. Courtesy of Paul Lucky, M.D.
77FF26.jpg|Fig. 77.26 Coccidioidomycosis. Moist erythematous
plaque on the face (A) and multiple papules and suppurative nodules on th
e arm (B) in two patients living in the southwestern US.
77FF27.jpg|Fig. 77.27 Life cycle of C. immitis.
77FF28.jpg|Fig. 77.28 Cutaneous features of common opportunistic
mycoses. While the lesions of opportunistic fungal infections seem non-speci
fic, certain presentations may be more likely associated with a particular speci
es.
77FF29.jpg|Fig. 77.29 Opportunistic fungal infections in immunoco
mpromised hosts. Primary cutaneous aspergillosis characterized by hyperpigme
nted plaques with brown-black scale crusts at the site of intravenous catheters
on the arm (A); firm pink papulonodule due to disseminated candidiasis (B); necrotic hemorrhagic bulla due to embolus of Aspergillus flavus
(C); and cellulitis due to Cryptococcus neoformans (D). A,
Courtesy of Jean Bolognia, M.D.; B, courtesy of Kalman Watsky, M.D.
77FF30.jpg|Fig. 77.30 Representative colonies of Trichophyton rub
rum (A), T. mentagrophytes var. mentagrophytes (B), T. mentagrophytes
var. interdigitale (C), T. tonsurans (D), Candida albicans (E)
and Rhizopus (F). A White cottony front and venous blood reve
rse; B tan granular front and tan reverse; C white cottony front a
nd buff to light yellow reverse; D tan suede front with furrows and mahog
any reverse; E creamy white colonies; F black woolly (fast growing
).
77FF31.jpg|Fig. 77.31 Cotton blue stain of T. tonsurans in cul
ture. Slender long macroconidia and microconidia of varying sizes.
77FF32.jpg|Fig. 77.32 KOH-chlorazol black stain of dermal scrapin
gs of embolic lesions of Rhizopus. Broad, non-septate hyphae with 90&
#176; branching.
77FT1.jpg|Table 77.1 Organization of cutaneous mycoses.
77FT2.jpg|Table 77.2 Superficial mycoses of the skin.
77FT3.jpg|Table 77.3 Comparison of black and white piedra6. *Sexual reproduction.

77FT4.jpg|Table 77.4 Dermatophytes isolated around the world
56. *On Sabouraud’s agar.
77FT5.jpg|Table 77.5 Types of dermatophytes based on mode of tran
smission.
77FT6.jpg|Table 77.6 Common dermatophytes that cause tinea corpor
is.
77FT7.jpg|Table 77.7 Differential diagnoses of dermatophyte infec
tions.
77FT8.jpg|Table 77.8 Tinea cruris: common causative pathogens
77FT9.jpg|Table 77.9 The four major types of ‘tinea pedis&#
8217; (including dematiaceous and dermatomycoses). *Because of the thickness
of stratum corneum on plantar surfaces and the inability of T. rubrum to
elicit an immune response sufficient to eliminate the fungus16. &#82
25;Often Pseudomonas, Proteus or Staphylococcus aureus. †All
ergic reaction to fungal elements presenting as a dyshidrotic-like eruption on t
he fingers and palms (culture-negative for fungus). CMI, cell-mediated immunity.
77FT10.jpg|Table 77.10 Non-dermatophyte molds that can cause onyc
homycosis.
77FT11.jpg|Table 77.11 Suggested systemic regimens for dermatophy
toses.
77FT12.jpg|Table 77.12 Colors of grains in eumycotic and actinomy
cotic mycetoma. *Most common cause in the US. **Rare. ***Rare cause of mycet
oma; causes actinomycosis (e.g. cervicofacial, thoracic, and abdominal) which al
so has draining sinuses and grains.
77FT13.jpg|Table 77.13 Differential diagnosis of parasitized macr
ophages2.
77FT14.jpg|Table 77.14 Infectious causes of a sporotrichoid patte
rn.
77FT15.jpg|Table 77.15 Treatment of opportunistic mycoses. Ap
propriate selection of therapy for opportunistic infections is essential given t
he likelihood of rapid, widespread dissemination and high mortality rates41
.
78FF1.jpg|Fig. 78.1 Estimated number of adults and children newly
infected with HIV during 2000. Data from Joint United Nations Programmes on
HIV/AIDS and World Health Organization .
78FF2.jpg|Fig. 78.2 Replication of human immunodeficiency virus w
ithin CD4+ lymphocyte and target sites of antiretroviral drugs.
78FF3.jpg|Fig. 78.3 Kinetics of viral load and immune response du
ring the phases of HIV-1 infection. After HIV-1 exposure, initial virus repl
ication and spread occur in the lymphoid organs, and systemic dissemination of H
IV-1 is reflected by the peak of plasma viremia. A clinical syndrome of varying
severity is associated with this phase of primary HIV-1 infection in up to 70% o
f HIV-1-infected persons. Downregulation of viremia during the transition from t
he primary to the early chronic phase coincides with the appearance of HIV-1-spe
cific cytotoxic T lymphocytes and with the progressive resolution of the clinica
l syndrome. The long phase of clinical latency is associated with active virus r
eplication, particularly in the lymphoid tissue. During the clinically latent pe
riod, CD4+ T-lymphocyte counts slowly decrease as does the HIV-1-spec
ific immune response. When CD4+ T-lymphocyte counts decrease below 20
0 cells/ml (i.e. when overt AIDS occurs), the clinical picture is characterized
by severe constitutional symptoms and by the possible development of opportunist
ic infections and/or neoplasms. Reproduced from Rizzardi GP, Pantaleo G. The imm
unopathogenesis of HIV-1 infection. In: Armstrong D, Cohen J. Infectious Disease
s. London: Mosby, 1999: 5.6.1–12.
78FF4.jpg|Fig. 78.4 Chronic ulcerative herpes simplex viral infec
tion in an HIV-infected patient. Slowly enlarging ulcers of the buttocks and
perianal area. Note the scalloping of the border.
78FF5.jpg|Fig. 78.5 Bacillary angiomatosis in an HIV-infected ind
ividual. Multiple red and purple papules and nodules are seen on the trunk.
78FF6.jpg|Fig. 78.6 Disseminated cryptococcosis in the setting of

AIDS. Several ulcers with rolled borders are seen. Microscopic examination
and culture of dermal scrapings or biopsy specimen confirm the diagnosis.
78FF7.jpg|Fig. 78.7 Severe psoriasis in a patient with AIDS.
Both sudden acute exacerbations and treatment resistance can be observed. Courte
sy of Yale Residents Slide Collection.
78FF8.jpg|Fig. 78.8 Eosinophilic folliculitis. Due to associa
ted pruritus, follicular papules are often excoriated; lesions favor the head an
d upper torso.
78FF9.jpg|Fig. 78.9 Zidovudine-associated melanonychia. Patie
nts receiving zidovudine may develop longitudinal streaks, horizontal bands and
diffuse hyperpigmentation.
78FF10.jpg|Fig. 78.10 Kaposi's sarcoma. Red-violet papules on
the palate in addition to oral candidiasis.
78FF11.jpg|Fig. 78.11 Aphthae major in a patient with AIDS. R
esolution of these lesions may require thalidomide. Courtesy of Yale Residents S
lide Collection.
78FF12.jpg|Fig. 78.12 Oral herpes simplex and oral candidiasis. Combination of oral herpes simplex and oral candidiasis in an otherwise healt
hy young man who proved to be HIV positive.
78FT1.jpg|Table 78.1 AIDS-defining criteria in patients infected
with HIV
78FT1.jpg|Table 78.1 AIDS-defining criteria in patients infected
with HIV
78FT2.jpg|Table 78.2 HIV risk factors
78FT3.jpg|Table 78.3 Correlation of CD4+ count with sp
ecific HIV-associated disorders
78FT4.jpg|Table 78.4 Differential diagnosis of mucocutaneous lesi
ons in HIV-infected patients on the basis of clinical appearance
78FT5.jpg|Table 78.5 Differential diagnosis of mucocutaneous lesi
ons in HIV-infected patients on the basis of anatomic distribution
78FT6.jpg|Table 78.6 Medications commonly used for HIV management
and associated adverse drug reactions
78FT7.jpg|Table 78.7 Change in prevalence of HIV-associated cutan
eous disorders with HAART
78FT8.jpg|Table 78.8 Effects of antiretroviral drugs on cytochrom
e P450
79FF1.jpg|Fig. 79.1 Initial visits to physicians' offices for gen
ital warts in the United States during the years 1966 to 1996. Adapted from:
National Disease and Therapeutic Index (IMS America, Ltd).
79FF2.jpg|Fig. 79.2 Doughnut of diagnoses. The incidence of H
PV-associated cervical pathologies in the United States is given. There is a dra
matic decline from the number of patients diagnosed with atypical squamous cells
of undetermined significance (ASCUS) to low-grade squamous intraepithelial lesi
ons (LSIL) to high-grade squamous intraepithelial lesions (HSIL) to cervical car
cinoma. Adapted from CDC, Division of STD Prevention8.
79FF3.jpg|Fig. 79.3 Transmission electron photomicrograph of puri
fied HPV-16 virus-like particles (VLP). These particles are currently in lat
e clinical trials as a potential prophylactic subunit vaccine. Following express
ion in cell culture, the L1 capsid protein self-assembles into VLP (empty capsid
s approximately 50 nm in diameter devoid of HPV DNA) that display type-spec
ific and neutralization surface epitopes similar to native virions. Courtesy of
Saeed Shafti-Keramat.
79FF4.jpg|Fig. 79.4 Genetic organization of the HPV-16 genome. The genome is drawn as a linearized map of the 7.9 kb circular double-str
anded genome. All open reading frames (ORF) reside on one strand. Early (E) and
late (L) regions are indicated. The upstream regulatory region (URR) contains th
e origin of replication and control elements for transcription and replication.
79FF5.jpg|Fig. 79.5 The papillomavirus life cycle. The figure
shows a productive (virion-producing) benign wart. Adapted from Orth .
79FF6.jpg|Fig. 79.6 Verrucae vulgares or common warts. Courte

sy of A Geusau, M.D.
79FF7.jpg|Fig. 79.7 Common wart. Absence of the nail plate ca
used by destruction of nail matrix and bed by a common wart.
79FF8.jpg|Fig. 79.8 Verrucae plantares or plantar warts. The
photo was taken after shaving of the hyperkeratotic surface; the black dots repr
esent thrombosed capillaries.
79FF9.jpg|Fig. 79.9 Myrmecial wart. The wart at the base of t
he distal phalanx of the hallux is painful due to deep endophytic growth; in add
ition there are confluent plaques of superficial warts (mosaic warts).
79FF10.jpg|Fig. 79.10 Extensive and chronic verrucosis of the sol
e causing pain when walking. HPV-2a was isolated from the lesions of this ot
herwise immunocompetent and healthy patient.
79FF11.jpg|Fig. 79.11 Verrucae planae or flat warts. The wart
s are skin colored to pink, smooth surfaced, flat papules (HPV-10 was detected).
79FF12.jpg|Fig. 79.12 Confluent scaly plaques resembling flat war
ts in a patient with EDV.
79FF13.jpg|Fig. 79.13 Generalized erythematous macules and plaque
s of EDV. These macules and plaques are from the same EV patient as shown in
& (lesions tested positive for HPV-8 and 36).
79FF14.jpg|Fig. 79.14 Multiple actinic keratoses and a squamous c
ell carcinoma of the upper cutaneous lip in a patient with EDV. Several bowe
noid cancers of the scalp were also present and skin grafts from multiple previo
us excisions are visible.
79FF15.jpg|Fig. 79.15 Condylomata acuminata or genital warts.
The warts are located on the prepuce and penis shaft.
79FF16.jpg|Fig. 79.16 Perianal condylomata acuminata. They ar
e macerated due to moisture from occlusion.
79FF17.jpg|Fig. 79.17 Bowenoid papulosis of the vulva (histol
ogically a vulvar intraepithelial neoplasia, VIN). Extensive red–brown or
whitish papules and plaques containing high-risk HPV in an HIV-positive patient.
Analogous high-grade squamous intraepithelial lesions (HSIL) were present peria
nally (AIN) and on the cervix (CIN).
79FF18.jpg|Fig. 79.18 Bowenoid papulosis of the anus positive for
high-risk HPV in a homosexual man. Histology revealed high-grade anal intra
epithelial neoplasia (AIN).
79FF19.jpg|Fig. 79.19 Erythroplasia of Queyrat. A well-demarc
ated velvety plaque of the prepuce positive for high-risk HPV; histology detecte
d a high-grade penile intraepithelial neoplasia (PIN).
79FF20.jpg|Fig. 79.20 Giant condylomata acuminata (Buschke–
Löwenstein tumor). Cauliflower-like, deeply infiltrating giant condylom
ata acuminata (Buschke–Löwenstein tumor) in an older woman.
79FF21.jpg|Fig. 79.21 Histology of Buschke–Löwenstein
tumor. There is downward extension of bulbous rete ridges without penetratio
n of the basement membrane and a lack of cellular atypia.
79FF22.jpg|Fig. 79.22 Histology of verruca vulgaris. Note the
characteristic features of ‘church spire’ papillomatosis heaped wit
h ortho- and parakeratosis, acanthosis, and koilocytosis. Courtesy of R Tyler, M
.D.
79FF23.jpg|Fig. 79.23 Histology of vulvar intraepithelial neoplas
ia (VIN). Note the characteristic features of abnormal keratinocyte maturati
on, nuclear pleomorphism, and dyskeratosis. Courtesy of R Tyler, M.D.
79FF24.jpg|Fig. 79.24 Extensive and therapy-resistant genital war
ts in a renal transplant patient.
79FF25.jpg|Fig. 79.25 Verrucous proliferative leukoplakia of the
oral cavity. The lesions have focally progressed to invasive squamous cell c
arcinoma; HPV DNA was not detectable by PCR.
79FF26.jpg|Fig. 79.26 Treatment of anogenital warts.
79FT1.jpg|Table 79.1 Clinical manifestations and associated HPV t
ypes.
79FT2.jpg|Table 79.2 Management of anogenital warts with grading

of recommendations. Grading of recommendation: (1), based on randomized, con
trolled trials of good quality and consistency; (2), well-conducted clinical stu
dies but no randomized clinical trials 67.
80FF1.jpg|Fig. 80.1 Basic pathogenesis of human herpesvirus infec
tions.
80FF2.jpg|Fig. 80.2 Primary herpes simplex virus type 2 infection
in a teenager. Note the scalloped borders. Courtesy of Jean Bolognia, M.D.
80FF3.jpg|Fig. 80.3 Herpes labialis with grouped vesicopustules.
80FF4.jpg|Fig. 80.4 Recurrent herpes simplex virus type 1 infecti
on on the cheek. Occasionally, such lesions are misdiagnosed as cellulitis.
Courtesy of Kalman Watsky, M.D.
80FF5.jpg|Fig. 80.5 Primary genital herpes. In addition to he
morrhagic crusts, there are perifollicular vesicopustules.
80FF6.jpg|Fig. 80.6 Primary genital herpes.
80FF7.jpg|Fig. 80.7 Eczema herpeticum in a child with atopic derm
atitis. Photograph courtesy of Harvey Blank, M.D.
80FF8.jpg|Fig. 80.8 Herpetic whitlow due to HSV-2.
80FF9.jpg|Fig. 80.9 Herpes simplex virus infections in immunocomp
romised hosts. Enlarging ulcerations in a child with acute lymphocytic leuke
mia who was presumed to have a Rhizopus infection (A) and a young man wit
h AIDS (B). Coalescence of lesions into a yellow-white plaque on the tong
ue (C).
80FF10.jpg|Fig. 80.10 Neonatal herpes due to HSV-2. Widesprea
d erosions and ulcerations are seen.
80FF11.jpg|Fig. 80.11 Varicella. Widespread lesions in differ
ent stages of development (A). Vesicles often develop central umbilicatio
n (B) and some lesions become pustular (C). A,B Courtesy of Robert
Hartman, M.D.
80FF12.jpg|Fig. 80.12 Herpes zoster. Ophthalmic zoster with s
harp midline demarcation of erythema and crusts on the forehead as well as contr
alateral periorbital edema (A). Bullous zoster on the arm (B).
80FF13.jpg|Fig. 80.13 Chronic verrucous zoster in an HIV-infected
patient.
80FF14.jpg|Fig. 80.14 Disseminated zoster with multiple necrotic
lesions on the feet.
80FF15.jpg|Fig. 80.15 Widespread erythematous macules associated
with use of ampicillin in a patient with infectious mononucleosis (due to the Ep
stein–Barr virus).
80FF16.jpg|Fig. 80.16 TORCH syndrome due to cytomegalovirus.
80FF17.jpg|Fig. 80.17 Retinitis due to cytomegalovirus in a patie
nt with AIDS.
80FF18.jpg|Fig. 80.18 Kaposi's sarcoma of the palm in a patient w
ith AIDS.
80FT1.jpg|Table 80.1 The eight human herpesviruses, their classif
ication and differential diagnoses.
80FT2.jpg|Table 80.2 Antiviral therapy for herpes simplex virus a
nd varicella zoster virus. Famciclovir is used to treat herpes labialis (usi
ng doses at or above those used for genital herpes) and famciclovir and valacycl
ovir are used to treat primary varicella (at doses used for shingles); valacyclo
vir is used to treat herpes simplex infections in immunocompromised persons (usi
ng doses at or above those used for genital herpes in immunocompetent persons) a
lthough these drugs are not specifically FDA approved for these indications.
80FT3.jpg|Table 80.3 EBV-associated serologies in infectious mono
nucleosis.
80FT4.jpg|Table 80.4 Cutaneous manifestations of CMV infections.
81FF1.jpg|Fig. 81.1 Relative size and shape of viruses infecting
humans. With permission from Hsiung's Diagnostic Virology, Yale Unive
rsity Press, 1994.

81FF2.jpg|Fig. 81.2 Approach to the patient with a presumed morbi
lliform or maculopapular viral exanthem.
81FF3.jpg|Fig. 81.3 Clinical manifestations of enterovirus infect
ion.
81FF4.jpg|Fig. 81.4 Hand-foot-and-mouth disease. Note the ova
l or football-shaped vesicle on an erythematous base centrally.
81FF5.jpg|Fig. 81.5 Enteroviral exanthem. Note prominent pete
chial component of the exanthem in this 10-year-old boy.
81FF6.jpg|Fig. 81.6 Measles. Pink macules and minimally eleva
ted papules with confluence.
81FF7.jpg|Fig. 81.7 Erythema infectiosum. Lacy, reticulated s
kin eruption over the arm during the second stage of the exanthem. Courtesy of Y
ale Residents Slide Collection.
81FF8.jpg|Fig. 81.8 Papular-purpuric gloves and socks syndrome. Erythematous patches with petechiae on the palms. This patient also had super
ficial erosions of the palate and pharynx.
81FF9.jpg|Fig. 81.9 Unilateral laterothoracic exanthem. Eryth
ematous macules and papules involving the left axilla, lateral trunk and flank.
The exanthem progressed to a bilateral distribution, but maintained left-sided p
redominance.
81FF10.jpg|Fig. 81.10 Gianotti–Crosti syndrome. Multipl
e, edematous erythematous papules of the extensor extremities.
81FF11.jpg|Fig. 81.11 Orf. Vesicopustule and ulceration on fi
nger.
81FF12.jpg|Fig. 81.12 Molluscum contagiosum. A Papules with c
entral umbilication. B Histologic section demonstrating multiple molluscu
m bodies.
81FF13.jpg|Fig. 81.13 Kawasaki disease. A Strawberry tongue a
nd cheilitis. Courtesy of Robert Hartman, M.D. B Perineal eruption of Kaw
asaki disease. Accentuation of erythema in the genital or perineal region is a c
haracteristic cutaneous finding.
81FT1.jpg|Table 81.1 Serologic assays of antibody responses.
CPE, cytopathic effect; Ab, antibody; Ag, antigen.
81FT2.jpg|Table 81.2 Parvovirus B19 clinical associations. *P
atients suffering from decreased red cell production (i.e. iron deficiency, thal
assemias) or increased red cell destruction (i.e. sickle cell anemia, hereditary
spherocytosis, pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase de
ficiency).
81FT3.jpg|Table 81.3 Potential etiologies reported in association
with Gianotti–Crosti syndrome. *Reported most commonly in Europe. &#1
67;Most common cause in United States. DPT, diphtheria–pertussis–tet
anus; MMR, measles–mumps–rubella.
81FT4.jpg|Table 81.4 Comparison of chickenpox/disseminated zoster
to smallpox.
81FT5.jpg|Table 81.5 Selected poxvirus infections.
81FT6.jpg|Table 81.6 Treatment of molluscum contagiosum. Key
to evidence-based support: 1, double-blind studies; 2, open-label series; 3, cas
e reports/anecdote.
81FT7.jpg|Table 81.7 Cutaneous manifestations of hepatitis B and/
or C infection
82FF1.jpg|Fig. 82.1 Comparison of trends in the number of reporte
d cases of syphilis in industrialized countries, 1970–1995.
82FF2.jpg|Fig. 82.2 Positive dark-field examination. Treponem
es are recognized by their characteristic corkscrew shape and deliberate forward
and backward movement with rotation about the longitudinal axis. From Morse et
al. Atlas of Sexually Transmitted Diseases and AIDS, 3rd edn. London: Mosby; 200
3.
82FF3.jpg|Fig. 82.3 Natural history of untreated syphilis. Ad
apted from Rein MF, Musher DM. Late syphilis. In: ReinMF (ed) Atlas of Infectiou
s Diseases, Vol V: Sexually Transmitted Diseases. New York: Current Medicine Ltd
. 1995,10.1–10.13.
82FF4.jpg|Fig. 82.4 Natural history of untreated syphilis.
82FF5.jpg|Fig. 82.5 Clinical manifestations of early syphilis. LI, syphilis I; LII, syphilis II; LIII, syphilis III. Adapted from Fritsch P,
Stary A, Trenkwalder B. Venerologie. In Fritsch P (ed). Dermatologie und Venerol
ogie. Berlin: Springer. 1998.
82FF6.jpg|Fig. 82.6 Chancre of primary syphilis. The lesion i
s firm to palpation. From Callen & Jorizzo (eds). Dermatological Signs of In
ternal Disease, 3rd edn. London: Saunders; 2003.
82FF7.jpg|Fig. 82.7 Secondary syphilis. Widespread exanthems
of pink papules (A,B) and obviously papulosquamous lesions (C). Le
sions on the palms (D) and soles (E) can have a collarette of scal
e. Courtesy of Yale Residents Slide Collection.
82FF8.jpg|Fig. 82.8 Orogenital lesions of secondary syphilis.
Oral lesions can vary from small superficial ulcers (A) to mucous patche
s (B). Condylomata lata (C) may be misdiagnosed as HPV infection (
condylomata acuminata). Courtesy of Yale Residents Slide Collection.
82FF9.jpg|Fig. 82.9 Less common manifestations of secondary syphi
lis. A Annular plaques of the forehead with central hyperpigmentation. B Granulomatous nodules and plaques. Courtesy of Yale Residents Slide Collecti
on.
82FF10.jpg|Fig. 82.10 Clinical manifestations of late syphilis. LI, syphilis I; LII, syphilis II; LIII, syphilis III. Adapted from Fritsch P,
Stary A, Trenkwalder B. Venerologie. In Fritsch P (ed). Dermatologie und Venero
logie. Berlin: Springer. 1998.
82FF11.jpg|Fig. 82.11 Clinical manifestations of congenital syphi
lis. LI, syphilis I; LII, syphilis II; LIII, syphilis III. Adapted from Frit
sch P, Stary A, Trenkwalder B. Venerologie. In Fritsch P (ed). Dermatologie und
Venerologie. Berlin: Springer. 1998.
82FF12.jpg|Fig. 82.12 Congenital syphilis. Red brown plaques
on the plantar surface. Courtesy of Yale Residents Slide Collection.
82FF13.jpg|Fig. 82.13 Specific and non-specific serologic tests f
or syphilis. Adapted from Fritsch P, Stary A, Trenkwalder B. Venerologie. In
Fritsch P (ed). Dermatologie und Venerologie. Berlin: Springer. 1998.
82FF14.jpg|Fig. 82.14 Incidence of gonorrhea in European countrie
s and the United States during the 1970s. Adapted from Fritsch P, Stary A, T
renkwalder B. Venerologie. In Fritsch P (ed). Dermatologie und Venerologie. Berl
in: Springer. 1998.
82FF15.jpg|Fig. 82.15 Pustular lesion on a necrotic base is repre
sentative of disseminated gonococcemia. Courtesy of Neil A Fenske, M.D. From
Callen & Jorizzo (eds). Dermatological Signs of Internal Disease, 3rd edn.
London: Saunders; 2003.
82FF16.jpg|Fig. 82.16 Diagnostic management in urethral discharge
or dysuria.
82FF17.jpg|Fig. 82.17 Gonorrhea. Gram-stained smear of urethr
al discharge containing numerous PMNs and Gram-negative intracellular diplococci
consistent with Neisseria gonorrhoeae. From Armstrong & Cohen (eds).
Infectious Diseases. London: Mosby; 1999.
82FF18.jpg|Fig. 82.18 Estimated worldwide prevalence of chancroid
.
82FF19.jpg|Fig. 82.19 Gram stain of exudate from genital ulcer sh
owing the ‘railroad track’ appearance of H. ducreyi.
82FF20.jpg|Fig. 82.20 Chancroid. A Well-demarcated painful ul
cers of the penis. B Unilateral lymphadenopathy with overlying erythema.
Courtesy of Yale Residents Slide Collection.
82FF21.jpg|Fig. 82.21 Erosive ulcerated lesion of granuloma ingui
nale. From Callen & Jorizzo (eds). Dermatologic Signs of Internal Diseas
e, 3rd edn. London: Saunders; 2003.
82FF22.jpg|Fig. 82.22 Worldwide distribution of donovanosis.

82FT1.jpg|Table 82.1 Sexually transmitted and transmissible patho
gens.
82FT2.jpg|Table 82.2 Classification of Treponemas.
82FT3.jpg|Table 82.3 Characteristics of Treponema pallidum.
82FT4.jpg|Table 82.4 Characteristics of secondary syphilis.
82FT5.jpg|Table 82.5 Classification of neurosyphilis. Adapted
from Merritt HH, et al. Neurosyphilis. New York: Oxford University Press. 194616.
82FT6.jpg|Table 82.6 Mother-to-child transmission and consequence
s.
82FT7.jpg|Table 82.7 Limitations of non-treponemal and treponemal
tests.
82FT8.jpg|Table 82.8 Differential diagnoses for syphilis.
82FT9.jpg|Table 82.9 Treatment recommendations for syphilis.
82FT10.jpg|Table 82.10 Treatment recommendations for syphilis for
special situations. *If neurosyphilis is excluded. **If neurosyphilis is no
t excluded.
82FT11.jpg|Table 82.11 Clinical manifestations of gonorrhea.
82FT12.jpg|Table 82.12 Treatment recommendations41–43.
82FT13.jpg|Table 82.13 Infectious causes of genital ulcer disease
.
82FT14.jpg|Table 82.14 Treatment regimens for chancroid.
82FT15.jpg|Table 82.15 Clinical manifestations of lymphogranuloma
venereum.
82FT16.jpg|Table 82.16 Treatment regimen for lymphogranuloma vene
reum.
82FT17.jpg|Table 82.17 Treatment regimen for donovanosis.
83FF1.jpg|Fig. 83.1 Distribution of visceral leishmaniasis. M
odified with permission from Davidson RN, Leishmaniasis. In Armstrong D, Cohen J
, eds, Infectious Diseases. London: Mosby, 1999.
83FF2.jpg|Fig. 83.2 Distribution of cutaneous leishmaniasis.
Modified with permission from Davidson RN, Leishmaniasis. In Armstrong D, Cohen
J, eds, Infectious Diseases. London: Mosby, 1999.
83FF3.jpg|Fig. 83.3 Life cycle of Leishmania species.
Promastigotes develop within the gut of the sandfly and then migrate to the prob
oscis.
83FF4.jpg|Fig. 83.4 Cutaneous leishmaniasis. A well circumscr
ibed ulcerated lesion on the face of a child.
83FF5.jpg|Fig. 83.5 Cutaneous leishmaniasis. Multiple ulcerat
ed lesions on the legs of a rural worker.
83FF6.jpg|Fig. 83.6 Cutaneous leishmaniasis. Circular scars a
t previous sites of cutaneous leishmaniasis are often the only sign of a previou
s infection.
83FF7.jpg|Fig. 83.7 Mucocutaneous leishmaniasis. There is ede
ma of the nose and focal deep ulceration of the area of the vestibule and upper
lip.
83FF8.jpg|Fig. 83.8 Disseminated leishmaniasis. Note the mult
iple erythematous plaques with scale-crust on the trunk.
83FF9.jpg|Fig. 83.9 Mucocutaneous leishmaniasis. Partial dest
ruction of the nasal cartilage, upper lip and palate, as well as infiltration of
the upper lip.
83FF10.jpg|Fig. 83.10 Leishmaniasis. Infiltrated ‘dry&#
8217; inflammatory plaques of leishmaniasis in a woman from the Calabria region
of Italy. Courtesy of Yale Residents Slide Collection.
83FF11.jpg|Fig. 83.11 Post kala-azar dermal leishmaniasis. Th
is syndrome is a sequel to visceral leishmaniasis that may arise several years a
fter the successful treatment of the primary Leishmania donovani infectio
n, as in this Indian woman. Dermal lesions vary greatly in appearance and may co
ntain amastigotes in large numbers. Some patients with hypopigmented macules may
serve as reservoirs for fresh epidemics if condition occur that favor sandfly b
reeding and transmission. With permission from Peters W, Pasvol G, Tropical Medi
cine and Parasitology, 5th edition. London: Mosby.
83FF12.jpg|Fig. 83.12 Post kala-azar dermal leishmaniasis nodules
. Nodules of various sizes, some pedunculated, are seen in this patient who
had been treated for kala-azar over a period of six months, 20 years previously.
With permission from Peters W, Pasvol G, Tropical Medicine and Parasitology, 5t
h edition. London: Mosby.
83FF13.jpg|Fig. 83.13 Amebiasis. Multiple large ulcers on the
legs of a patient with cutaneous amebiasis. Note the extensive tissue destructi
on and resemblance to pyoderma gangrenosum.
83FF14.jpg|Fig. 83.14 Distribution map of Chagas' disease and Afr
ican trypanosomiasis. Adapted with permission from Peters W, Pasvol G, Tropi
cal Medicine and Parasitology, 5th edition. London: Mosby.
83FF15.jpg|Fig. 83.15 Life cycle of Trypanosoma cruzi.
Modified with permission from Keusch GT, Host response to infection. In: Armstr
ong D, Cohen J, eds, Infectious Diseases. London: Mosby, 1999.
83FF16.jpg|Fig. 83.16 Chagas disease. Young child with unilat
eral periorbital edema characteristic of this disease (Romaña sign).
83FF17.jpg|Fig. 83.17 Apical aneurysm of the heart. Mural thr
ombi may be present at the apex of the left ventricle, with marked thinning of b
oth ventricular walls. Apical aneurysm formation is commonly seen. With permissi
on from Peters W, Pasvol G, Tropical Medicine and Parasitology, 5th edition. Lon
don: Mosby.
83FF18.jpg|Fig. 83.18 Radiograph of megaesophagus. Muscular d
egeneration and devervation of segments of the alimentary tract through destruct
ion of the cells of Auerbach's plexus cause megaesophagus, megastomach and megac
olon, which can be detected radiologically. With permission from Peters W, Pasvo
l G, Tropical Medicine and Parasitology, 5th edition. London: Mosby.
83FF19.jpg|Fig. 83.19 African trypanosomiasis. Life cycle of
T. brucei in humans and reservoir hosts.
83FF20.jpg|Fig. 83.20 Trypanosomal chancre. The bite reaction
, the earliest clinical lesion, is known as a ‘trypanosomal chancre’
. It resembles a boil but is usually painless. Fluid aspirated from the nodule c
ontains actively dividing trypanosomes. This reaction is seen more commonly in rhodesiense than in gambiense infection. With permission from Peter
s W, Pasvol G, Tropical Medicine and Parasitology, 5th edition. London: Mosby.
83FF21.jpg|Fig. 83.21 Life cycle of T. gondii. There i
s a wide range of mammalian hosts, the most important being the domestic cat. Mo
dified from Peters W, Pasvol G, Tropical Medicine and Parasitology, 5th edition.
London: Mosby.
83FF22.jpg|Fig. 83.22 Cutaneous larvae migrans. Note the char
acteristic serpiginous erythematous tracks between the toes (A) and on th
e foot (B). Vesicobullae can also be seen (C). Courtesy of Kalman
Watsky, M.D.
83FF23.jpg|Fig. 83.23 Living microfilariae of Onchocerca vovul
us. After some time, actively moving microfilariae emerge from the skin
snip into the surrounding saline where they can be counted. With permission from
Peters W, Pasvol G, Tropical Medicine and Parasitology, 5th edition. London: Mo
sby.
83FF24.jpg|Fig. 83.24 Distribution of onchocerciasis. The dis
ease is usually found in Africa and Central and South America.
83FF25.jpg|Fig. 83.25 Onchocerciasis. Diffuse lichenification
and hyperpigmentation in a patient with intense pruritus. Focal areas of leukod
erma are also present.
83FF26.jpg|Fig. 83.26 Onchocerciasis. Extraction of adult wor
ms from an onchocercoma on the scalp.
83FF27.jpg|Fig. 83.27 Life cycles of important human flukes: adul
ts living in the liver, lungs, intestines and blood. Modified with permissio
n from Cross JH, Helminths. In Armstrong D, Cohen J, eds, Infectious Diseases. L
ondon: Mosby, 1999.
83FF28.jpg|Fig. 83.28 Distribution of schistosomiasis. Adapte
d from Peters W, Pasvol G, Tropical Medicine and Parasitology, 5th edition. Lond
on: Mosby.
83FF29.jpg|Fig. 83.29 Swimmer's itch. Numerous edematous dark
red papules on the feet and ankles. Courtesy of Kalman Watsky, M.D.
83FF30.jpg|Fig. 83.30 Life cycles of important human roundworms:
adults living in tissues. With permission from Cross JH, Helminths. In Armst
rong D, Cohen J, eds, Infectious Diseases. London: Mosby, 1999.
83FF31.jpg|Fig. 83.31 Life cycles of important human roundworms:
adults living in the intestines. With permission from Cross JH, Helminths. I
n Armstrong D, Cohen J, eds, Infectious Diseases. London: Mosby, 1999.
83FF32.jpg|Fig. 83.32 Life cycles of important human tapeworms: a
dults living in tissue intestines and blood. Modified with permission from C
ross JH, Helminths. In Armstrong D, Cohen J, eds, Infectious Diseases. London: M
osby, 1999.
83FF33.jpg|Fig. 83.33 Life cycle of Trichinella spiralis. This nematode is a zoonotic infection that circulates between rats and vario
us carnivores. Trichinosis in humans commonly results from eating raw or inadequ
ately cooked prok products such as sausages. Infection is acquired by eating mus
cle containing encysted larvae which migrate from the GI tract through tissues t
o reach skeletal muscles in which they then encyst. With permission from Peters
W, Pasvol G, Tropical Medicine and Parasitology, 5th edition. London: Mosby.
83FF34.jpg|Fig. 83.34 Life cycle of Toxocara canis. Th
is demonstrates the importance of transplacental transmission in maintaining can
ine infection, and the role of young dogs in transmitting infection to humans. W
ith permission from Gillespie S, Migrating worms. In Armstrong D, Cohen J, eds,
Infectious Diseases. London: Mosby, 1999.
83FT1.jpg|Table 83.1 The genus Leishmania and the leishman
iases. Cutaneous and mucocutaneous disease.
83FT2.jpg|Table 83.2 The genus Leishmania and the leishman
iases—systemic disease.
83FT3.jpg|Table 83.3 Features of visceral leishmaniasis (L. do
novani). The duration of symptoms is 2 to 4 months, but is shorter in ch
ildren. With permission from Davidson RN, Leishmaniasis. In Armstrong D, Cohen J
, eds, Infectious Diseases. London: Mosby, 1999.
83FT4.jpg|Table 83.4 Major studies of antimonials for Leishman
iasis.
83FT5.jpg|Table 83.5 Other forms of therapy for Leishmaniasis.
83FT6.jpg|Table 83.6 Major parasitic worms that cause diseases an
d cutaneous manifestations in humans.
84FF1.jpg|Fig. 84.1 Elderly patient with scabies misdiagnosed as
eczema. Scabies incognito in which a patient with neuropathy demonstrated a
nonspecific hand rash without symptoms that proved to be due to scabietic mite.
84FF2.jpg|Fig. 84.2 Female scabies mite with egg. The female
scabies mite under potassium hydroxide wet mount obtained from skin scrapings re
vealing flattened, oval body with wrinkle-like corrugations, eight short legs, a
nd an egg ready for deposition. ×40. Used with permission from Taplin D, Me
inking TL. Infestations. In: Schachner LA, Hansen RC, eds. Pediatric Dermatology
. 2nd edn. Vol. 2. Edinburgh: Churchill Livingstone, 1995:1347–92.
84FF3.jpg|Fig. 84.3 The life cycle of the scabies mite.
84FF4.jpg|Fig. 84.4 Erythematous papules, linear burrows and area
s of crusting in an infant with scabies.
84FF5.jpg|Fig. 84.5 Direct microscopy of scraping from a patient,
demonstrating eggs and scybala.
84FF6.jpg|Fig. 84.6 Head louse family. Used with permission f
rom Taplin D, Meinking TL. Infestations. In: Schachner LA, Hansen RC, eds. Pedia
tric Dermatology. 2nd edn. Vol. 2. Edinburgh: Churchill Livingstone, 1995:1347&#

8211;92.
84FF7.jpg|Fig. 84.7 Head louse life cycle.
84FF8.jpg|Fig. 84.8 Head lice. A The head louse egg or nit is
0.8 mm in length. B Head lice nits on hair. Used with permission fr
om Taplin D, Meinking TL. Infestations. In: Schachner LA, Hansen RC, eds. Pediat
ric Dermatology. 2nd edn. Vol. 2. Edinburgh: Churchill Livingstone, 1995:1347&#8
211;92.
84FF9.jpg|Fig. 84.9 Crab lice. A Adult crab louse. Respirator
y spiricles and circulatory system are easily seen. Courtesy of Tony Burns, MD.
×45. B P. pubis of eyelashes. Used with permission from Tapli
n D, Meinking TL. Infestations. In: Schachner LA, Hansen RC, eds. Pediatric Derm
atology. 2nd edn. Vol. 2. Edinburgh: Churchill Livingstone, 1995:1347–92.
84FF10.jpg|Fig. 84.10 Body lice in the seams of clothing.
84FF11.jpg|Fig. 84.11 Tunga penetrans in a child.
84FF12.jpg|Fig. 84.12 Life cycle of Dermatobia hominis in
cutaneous myiasis. Courtesy of Yale Residents Slide Collection.
84FT1.jpg|Table 84.1 Treatment for scabies. All treatments fo
r scabies should be repeated 12–14 days later to kill any nymphs that surv
ived treatment and also to prevent the development of resistance.
84FT2.jpg|Table 84.2 Treatments for head lice. All treatments
should be given on two separate occasions, one week apart.
84FT3.jpg|Table 84.3 Treatment for crab lice. All crab lice t
reatments should be given on two separate occasions, one week apart
85FF1.jpg|Fig. 85.1 Bullous bug bites in a teenager.
85FF2.jpg|Fig. 85.2 Histologic section demonstrating a bee stinge
r and foreign body reaction.
85FF3.jpg|Fig. 85.3 Bedbugs.
85FF4.jpg|Fig. 85.4 Triatome bug.
85FF5.jpg|Fig. 85.5 Pulex irritans.
85FF6.jpg|Fig. 85.6 Megalopyge opercularis.
85FF7.jpg|Fig. 85.7 Characteristic train track hemorrhage associa
ted with M. opercularis.
85FF8.jpg|Fig. 85.8 Tick granuloma with persistent nodule at site
of tick bite on the scalp of a child.
85FF9.jpg|Fig. 85.9 Lone star ticks.
85FF10.jpg|Fig. 85.10 Dermacentor variabilis (engorged fem
ale).
85FF11.jpg|Fig. 85.11 Rhipicephalus ticks.
85FF12.jpg|Fig. 85.12 Ixodes tick.
85FF13.jpg|Fig. 85.13 Cheyletiella bites.
85FF14.jpg|Fig. 85.14 Brown recluse spider.
85FF15.jpg|Fig. 85.15 Brown recluse spider bite with central dusk
y necrosis.
85FF16.jpg|Fig. 85.16 Centipede bite.
85FF17.jpg|Fig. 85.17 Seabather's eruption with edematous pink pa
pules in the same distribution as the bathing trunks. Courtesy of Kalman Wat
sky, M.D.
85FF18.jpg|Fig. 85.18 ‘Scorpion’ fish include lionfis
h, zebrafish, bullrout, stonefish and waspfish.
85FT1.jpg|Table 85.1 Tick control measures
85FT2.jpg|Table 85.2 Mite families
85FT3.jpg|Table 85.3 Mites of medical importance
86FF1.jpg|Fig. 86.1 Depth of penetration of different wavelengths
of ultraviolet (UV) light into human skin. Depth of penetration varies grea
tly with the thickness of the different skin layers and their composition (e.g.
melanin content). The beginning of the wedge-shaped portion of the penetration s
ymbol represents a decrease to approximately one-third of the incident energy de
nsity, and the tip of the symbol a decrease to approximately 1%. Figure not draw
n to scale.
86FF2.jpg|Fig. 86.2 Sunburn. 24 hours after an accidental 10fold overdose of UVB prescribed as phototherapy. With permission, Department of
Dermatology, University of Würzburg, Germany.
86FF3.jpg|Fig. 86.3 Unilateral photoaging following 15 years of u
nilateral sun exposure through window glass. This individual had been workin
g in the same office for 15 years, close to a window, with the left cheek always
facing the window. Biopsy confirmed the diagnosis of nodular cutaneous elastosi
s with cysts and comedones (Favre–Racouchot disease). Since UVB does not p
enetrate window glass, this observation identifies UVA as an effective agent in
photoaging. Reproduced with permission from Moulin G, Thomas L, Vigneau M, Fiere
A. Un cas unilateral d'élastose avec kystes et comédons de Favre et R
acouchot. Ann Dermatol Venereol. 1994;121:721–3.
86FF4.jpg|Fig. 86.4 Sunburn freckles (solar lentigines). This
patient developed irregular, hyperpigmented macules confined to areas of a pron
ounced, non-blistering sunburn 6 months earlier. These irreversible lesions repr
esent early changes of photoaging. With permission, Department of Dermatology, U
niversity of Würzburg, Germany.
86FF5.jpg|Fig. 86.5 Photo-carcinogenesis cascade. This leads
from sun exposure of the skin to the formation of skin cancer.
86FF6.jpg|Fig. 86.6 Thymine dimer. Following excitation of th
e bases by short-wave UV light (UVB), a cyclobutane–pyrimidine dimer is fo
rmed by covalent linkage between two adjacent pyrimidines (here two thymine base
s) and formation of a cyclobutyl ring.
86FF7.jpg|Fig. 86.7 A pyrimidine–pyrimidone 6,4-photoproduc
t. A pyrimidine–pyrimidone (6–4) photoproduct is formed by coval
ent linkage between C-6 and C-4 of two adjacent pyrimidines (here a thymine and
a cytosine base), following excitation of the bases by short-wave UV light (UVB)
.
86FF8.jpg|Fig. 86.8 A wavelength of 300 nm is more effective
than one of 290 nm in inducing thymine dimers in the basal layer of the hu
man epidermis. After irradiation of human skin with monochromatic 290 n
m UVB (2 MED) and staining with anti-thymine dimer antibodies, most cells in the
basal layer show only blue counterstaining, while suprabasal layers demonstrate
pronounced reactivity. In contrast, with 2 MED of monochromatic 300 nm UVB
, a pronounced immunostaining is also evident in the basal layer of the epidermi
s. (Reproduced with permission from Young AR, Chadwick CA, Harrison GI, et al. T
he similarity of action spectra for thymine dimers in human epidermis and erythe
ma suggests that DNA is the chromophore for erythema. J Invest Dermatol. 1998;11
1:982–8.)
86FF9.jpg|Fig. 86.9 7-Hydro-8-oxyguanosine. 7,8-dihydro-8-oxy
guanosine (tautomer: 8-hydroxyguanosine) is an oxidation product of guanosine. I
t is formed by singlet oxygen, which is generated through a photosensitized reac
tion after excitation of a cellular chromophore by UVA.
86FF10.jpg|Fig. 86.10 Action spectrum for the induction of cyclob
utane dimers and oxidative guanine modifications in chinese hamster ovary (CHO)
cells. The number of DNA lesions was assessed by the ability of repair enzym
es to incise DNA from cells irradiated with different wavelengths from a monochr
omator. The ability of ultraviolet light to induce cyclobutane dimers and oxidat
ive DNA damage rapidly declines with increasing wavelengths. E.g., 320 nm u
ltraviolet light is approximately 1000-fold less capable of inducing cyclobutane
dimers than 290 nm ultraviolet light. This decline parallels well with the
decline of skin cancer formation in mice from 300 to 340 nm (Utrecht-Phila
delphia skin cancer action spectrum8 ). This decline does not mean th
at longer wavelengths do not contribute to photocarcinogenesis, because longerwa
ve UVA is much more abundant in natural sunlight than UVB, which offsets at leas
t some of the weaker effects of UVA. The second peak of oxidative base damage fo
rmation in the UVA range parallels with a second peak of skin cancer formation a
t 380 nm8 . Since there is no second peak of cyclobutane dimer f
ormation with UVA, this might indicate that oxidative base damage contributes mo
re to skin cancer formation with UVA.
86FF11.jpg|Fig. 86.11 Patient with xeroderma pigmentosum. UVexposed areas show the typical, irregular hypo- and hyperpigmented macules and s
urgical excision sites (more than 200 BCCs and SSCs had been removed). The nodul
e above the right lip was diagnosed as an amelanotic melanoma metastasis. With p
ermission, Department of Dermatology, University of Göttingen, Germany.
86FF12.jpg|Fig. 86.12 Nucleotide excision repair in non-transcrib
ed regions (global genome repair). This pathway repairs ‘bulky’
DNA lesions, such as pyrimidine dimers. A DNA damage recognition by XPC.
B Formation of an open bubble around the lesion by the helicase activity
of XPB and XPD. C Incision 5′ and 3′ of the lesion by the end
onucleases XPF and XPG. D Repair synthesis and gap closing after release
of a 24- to 34-residue oligonucleotide. LIG1, DNA ligase 1; PCNA, proliferating
cell nuclear antigen; RPA, replication protein A; TFIIH, transcription factor II
H. Adapted with permission from ref.2
86FF13.jpg|Fig. 86.13 The photocarcinogenesis cascade: prevention
and diseases with failure of prevention. Several intrinsic mechanisms prote
ct against the formation of skin cancer following UV exposure at different point
s of the photocarcinogenesis cascade of events. These mechanisms are impaired in
disorders with increased risk for UV-induced skin cancer. Each step of the phot
ocarcinogenesis cascade can be targeted for modification and reduction of skin c
ancer risk. Mechanisms that protect against or prevent the photocarcinogenesis c
ascade, and disorders that predispose to skin cancer because of impaired intrins
ic protective mechanisms.
86FT1.jpg|Table 86.1 Deficient DNA repair genes. Deficient DN
A repair genes in xeroderma pigmentosum (XP) complementation groups XPA to XPG,
trichothiodystrophy (TDD), Cockayne syndrome (CS), and xeroderma pigmentosum var
iant (ERCC1, excision repair cross complementing gene 1; NER, nucleotide excisio
n repair; TFIIH, transcription factor IIH).
87FF1.jpg|Fig. 87.1 Guide to the diagnosis of cutaneous photosens
itivity. The diagnosis can generally be made from patient history and clinic
al findings, provided the lupus titers are normal.
87FF2.jpg|Fig. 87.2 Polymorphous light eruption of the face.
The eruption is less red and confluent than is a sunburn.
87FF3.jpg|Fig. 87.3 Polymorphous light eruption of the lower arm. The patchiness of the edematous papules and plaques is characteristic.
87FF4.jpg|Fig. 87.4 Polymorphous light eruption of the abdomen. The lesions are typically papular and clustered.
87FF5.jpg|Fig. 87.5 Polymorphous light eruption. The histolog
y shows the characteristic perivascular mononuclear cell infiltration.
87FF6.jpg|Fig. 87.6 Actinic prurigo. The clinical features ar
e somewhat suggestive of polymorphous light eruption, but the lesions are persis
tent and the HLA type was that of actinic prurigo.
87FF7.jpg|Fig. 87.7 Actinic prurigo. The arms show crusted pa
pules that are denser distally; they are also worse in summer.
87FF8.jpg|Fig. 87.8 Actinic prurigo. This case of severe acti
nic prurigo shows spread to the buttocks.
87FF9.jpg|Fig. 87.9 Actinic prurigo. The pathology of this ol
der lesion shows epidermal hyperplasia and scale-crust, but an overall non-speci
fic picture.
87FF10.jpg|Fig. 87.10 Hyroa vacciniforme. There is an early,
polymorphous light eruption-like appearance, but with vesicles around the mouth
and umbilicated lesions on the nose.
87FF11.jpg|Fig. 87.11 Hydroa vacciniforme. A later, more seve
re example shows vesiculation with umbilication, but also marked hemorrhagic cru
sting.
87FF12.jpg|Fig. 87.12 Hydroa vacciniforme. A severe example o
f the typical vacciniform facial scarring that may develop following repeated ac
ute attacks.
87FF13.jpg|Fig. 87.13 Chronic actinic dermatitis. Somewhat in
filtrated dermatitis of the face that is worse in the summer.
87FF14.jpg|Fig. 87.14 Chronic actinic dermatitis. Lichenified

eczematous changes of the posterior neck with a sharp cut-off at the collar in
a patient with type V skin.
87FF15.jpg|Fig. 87.15 Chronic actinic dermatitis. Lichenified
eczematous changes of the dorsal aspects of the hands in a woman; proximal to t
he wrist, the lesions were less severe.
87FF16.jpg|Fig. 87.16 Solar urticaria. Sunlight-induced wheal
ing with surrounding erythema of the abdomen.
87FF17.jpg|Fig. 87.17 Exogenous drug-induced photosensitivity and
hyperpigmentation. Gray-brown reticulated patches on the sun-exposed skin o
f a patient receiving diltiazem; note the sparing of the upper pinna, usually co
vered by hair.
87FF18.jpg|Fig. 87.18 Exogenous chemical-induced photosensitivity
. This schematic demonstrates the interpretation of photopatch tests.
87FF19.jpg|Fig. 87.19 Endogenous chemical-induced photosensitivit
y. The pathophysiology of phototoxicity as seen in the cutaneous porphyrias
is shown.
87FF20.jpg|Fig. 87.20 Photoaggravated atopic eczema induced with
the solar simulator. This was the appearance seen 24 hours after irradiation
.
87FF21.jpg|Fig. 87.21 Cutaneous signs of significant photoaging.
A Cutis rhomboidalis nuchae with deep furrowing of the posterior neck. B Multiple open comedones of the malar region in Favre-Racouchot syndrome. 
C Erosive pustular dermatosis of the bald scalp.
87FT1.jpg|Table 87.1 Classification of photodermatoses.
87FT2.jpg|Table 87.2 Classification of idiopathic, probably immun
ologically based, photodermatoses.
87FT3.jpg|Table 87.3 Characteristics of the defective DNA repair
diseases. AD, autosomal dominant; AR, autosomal recessive.
87FT4.jpg|Table 87.4 Common phototoxic and photoallergic agents.
87FT5.jpg|Table 87.5 The photoaggravated dermatoses.
88FF1.jpg|Fig. 88.1 Thermal burn. This superficial second deg
ree burn is characterized by bullae that contain serous fluid. Courtesy of Kalma
n Watsky, M.D.
88FF2.jpg|Fig. 88.2 Rule of nines. In adults, an estimate of
burn extent is often based upon this surface area distribution chart. Infants an
d children have a relatively increased head: trunk surface area ratio.
88FF3.jpg|Fig. 88.3 Erythema ab igne. Reticulated hyperpigmen
tation with some epidermal atrophy and scaling is secondary to use of a heating
pad.
88FF4.jpg|Fig. 88.4 First degree frostbite. Erythema, edema a
nd hemorrhage are seen on the fingertips.
88FF5.jpg|Fig. 88.5 Pernio. Areas of violaceous discoloration
on the plantar surface of the foot and toes. Courtesy of Ron Rapini, M.D.
88FF6.jpg|Fig. 88.6 Electrical burn. It is characterized by e
rythema, edema, bulla formation and sloughing of the necrotic epidermis. Courtes
y of Timothy Givens, M.D.
88FF7.jpg|Fig. 88.7 Pathology of an electrical burns. Blister
ing seen in a biopsy from a patient who died of an electrical burn. Notice the e
longated keratinocyte nuclei. Courtesy of Ron Rapini, M.D.
88FF8.jpg|Fig. 88.8 Cutaneous manifestations of exposure to arsen
ic. A Guttate hypopigmentation superimposed on hyperpigmentation resembles &
#8216;raindrops on a dusty road.’ B Arsenical keratoses on the plan
tar surface. A, Courtesy of John Steinbaugh, M.D.
88FF9.jpg|Fig. 88.9 Black palm. This black color is due to he
moglobin within the thickened stratum corneum. Courtesy of Jean Bolognia, M.D.
88FF10.jpg|Fig. 88.10 Chondrodermatitis nodularis helicis. A
This red-dome-shaped nodule with a central keratin-filled crater is exquisitely
tender to palpation. The antihelical location is most characteristic in women. B Central crust, epithelial hyperplasia, fibrosis, granulation tissue and

degenerated cartilage are seen on histologic examination. Courtesy of Ron Rapini
, M.D.
88FF11.jpg|Fig. 88.11 Acanthoma fissuratum. This is a firm no
n-tender erythematous keratotic plaque with a vertical groove signifying the poi
nt of spectacle frame pressure. Courtesy of Ron Rapini, M.D.
88FF12.jpg|Fig. 88.12 Chronic ‘tennis toe’. Chron
ic and repeated trauma of the longer second toe against the end of the tennis sh
oe toe box during sudden stops creates the distal callus formation and nail plat
e thickening known as tennis toe.
88FF13.jpg|Fig. 88.13 Piezogenic papules. Yellowish outpouchi
ngs on the heel represent herniation of subcutaneous fat through the plantar fas
cia in this sometimes painful condition.
88FT1.jpg|Table 88.1 Heat-related illnesses1,3. Cu
taneous features are indicated in bold. T, temperature; BP, blood pressure; N/V,
nausea and vomitting; DIC, disseminated intravascular coagulation; AST, asparta
te transaminase.
88FT2.jpg|Table 88.2 Heat sources reported to cause erythema ab i
gne11,12,13,15.
88FT3.jpg|Table 88.3 Four stages of frostbite26
88FT4.jpg|Table 88.4 Causes of unintentional hair discoloration<s
up>50–53. *Speculative
88FT5.jpg|Table 88.5 Toxic and heavy metals and their cutaneous i
mpact55–63. *Concentration posing immediate danger to life
and health. Since 1979, NIOSH has not allowed detectable levels of known carcino
gens. Therefore there are no values in the IDLH column for carcinogens.
88FT6.jpg|Table 88.6 Cutaneous infections in athletes90&#821
1;92,94–96,101.
88FT7.jpg|Table 88.7 Allergic contact dermatitis associated with
musical instruments104,107.
89FF1.jpg|Fig. 89.1 Abuse of illicit and prescription drugs.
Estimates of current abuse of illicit and prescription drugs in the US during 20
00.
89FF2.jpg|Fig. 89.2 Injection sites in an intravenous drug user. Both linear hemorrhagic crusts are seen as well as hyperpigmented skin tract
s. Courtesy of Ron Rapini, M.D.
89FF3.jpg|Fig. 89.3 Skin popping scars. Circular depressed &#
8216;skin pop’ scars on the dorsae of the fingers and hands.
89FF4.jpg|Fig. 89.4 Atrophic depression and extensive calcificati
on of the buttock from chronic abuse of pentazocine injections (this patient was
reported by Magee et al.35).
89FF5.jpg|Fig. 89.5 Necrotizing fasciitis of the upper extremity
with erythema and extensive tissue necrosis in an intravenous heroin user.
89FF6.jpg|Fig. 89.6 Granuloma developing in a skin pop scar from
previous injection of adulterated heroin.
89FF7.jpg|Fig. 89.7 Missing and carious teeth and inflamed gums a
re common physical findings in hard core drug addicts.
89FF8.jpg|Fig. 89.8 Healing ulcer on the buttock due to prolonged
coma from barbiturate overdose.
89FT1.jpg|Table 89.1 Criteria for drug dependence1.
89FT2.jpg|Table 89.2 Cutaneous signs of drug abuse.
89FT3.jpg|Table 89.3 Drug-induced cutaneous reactions.
90FF1.jpg|Fig. 90.1 Bruising and petechiae. A, B Bruising and
petechiae of the pinna and post-auricular area in a 6-year old boy consistent w
ith a hand slap by an adult. C Complex bruising of the buttocks in a 3-we
ek old infant. From Hobbs CJ, Wynne JM. Physical Signs of Child Abuse. © 20
01 WB Saunders.C Complex bruising of the buttocks in a 3-week old infant.
90FF2.jpg|Fig. 90.2 Curvilinear mark on the cheek of a child from
assault with an electric cord.
90FF3.jpg|Fig. 90.3 Slap mark on the cheek. Ecchymoses which

outline the fingers often can be matched to the perpetrator's hand.
90FF4.jpg|Fig. 90.4 Healing injury due to binding around the ankl
es.
90FF5.jpg|Fig. 90.5 Injury produced by a cigarette burn.
90FF6.jpg|Fig. 90.6 Branding injury on the thigh from a fork.
90FF7.jpg|Fig. 90.7 Burn injury due to an iron. Courtesy of Y
ale Residents Slide Collection.
90FF8.jpg|Fig. 90.8 Burn injury due to dunking in hot water by th
e father. Courtesy of Leo Litter, M.D.
90FF9.jpg|Fig. 90.9 This unfortunate child was sexually abused. Courtesy of Ron Rapini, M.D.
90FT1.jpg|Table 90.1 Physical signs of childhood sexual abuse.
91FF1.jpg|Fig. 91.1 Langerhans cell histiocytosis (Letterer&#8211
;Siwe variant). Typical seborrheic dermatitis-like eruption of the scalp. Mu
ltiple confluent small crusted papules with petechiae. Courtesy of Johns Hopkins
School of Medicine Dermatlas, http://162.129.72.40/derm/
91FF2.jpg|Fig. 91.2 Langerhans cell histiocytosis (Letterer&#8211
;Siwe variant). Erosive plaques in the inguinal creases as well as erythemat
ous plaques. Courtesy of Johns Hopkins School of Medicine Dermatlas, http://162.
129.72.40/derm/
91FF3.jpg|Fig. 91.3 Langerhans cell histiocytosis (eosinophilic g
ranuloma of the bone). Radiography of the femur shows a large well-circumscr
ibed osteolytic lesion. Courtesy of Edward McCarthy, MD, Johns Hopkins Pathology
.
91FF4.jpg|Fig. 91.4 Langerhans cell histiocytosis. Superficia
l dermal infiltrate of pleomorphic LCH cells. Many nuclei, as seen in the inset,
show a classic reniform shape.
91FF5.jpg|Fig. 91.5 Immunohistochemistry of the histiocytoses.
91FF6.jpg|Fig. 91.6 Langerhans cell histiocytosis (Birbeck granul
es). Electron micrograph demonstrates classic racquet-shaped Birbeck granule
s in the cytoplasm of an LCH cell.
91FF7.jpg|Fig. 91.7 Benign cephalic histiocytosis. Multiple b
rown papules on the face of a young child.
91FF8.jpg|Fig. 91.8 Generalized eruptive histiocytoma. Multip
le firm red papules.
91FF9.jpg|Fig. 91.9 Juvenile xanthogranuloma. Red–yello
w and brownish nodule that had been present for 5 months. Courtesy of Anthony Ma
ncini, MD.
91FF10.jpg|Fig. 91.10 Juvenile xanthogranuloma. Dermal histio
cytic infiltrate mixed with lymphocytes and scattered Touton giant cells. Touton
giant cells have a ‘wreath-like’ arrangement of nuclei within the c
ell. Identical histologic findings are seen in xanthoma disseminatum.
91FF11.jpg|Fig. 91.11 Necrobiotic xanthogranuloma. Infiltrate
d and ulcerated yellow–red plaques on the eyelids and face of a patient wi
th necrobiotic xanthogranuloma. Prominent scarring is evident. Courtesy of Grant
J Anhalt, MD, Johns Hopkins Dermatology.
91FF12.jpg|Fig. 91.12 Necrobiotic xanthogranuloma. A necrobio
tic area contains cholesterol clefts. Surrounding this area are many bizarre mul
tinucleated giant cells.
91FF13.jpg|Fig. 91.13 Multicentric reticulohistiocytosis. Gro
uped firm red–brown papules on the dorsal surface of the fingers, hand and
wrist in this 73-year-old African–American woman. Courtesy of Susan D Lam
an, MD, Johns Hopkins Dermatology.
91FF14.jpg|Fig. 91.14 Reticulohistiocytosis. Light microscopy
: numerous mononucleated and multinucleated histiocytes extending from the papil
lary tips into the deep dermis. These histiocytes have abundant eosinophilic, fi
nely granular cytoplasm, creating a ‘ground glass’ appearance.
91FF15.jpg|Fig. 91.15 Cutaneous Rosai–Dorfman disease.

Discrete, dome-shaped papules.
91FF16.jpg|Fig. 91.16 Rosai–Dorfman disease. Large hist
iocytes are located inside a dermal lymphatic. Surrounding the lymphatic are num
erous histiocytes and groups of lymphocytes. The inset shows a histiocyte which
has engulfed several lymphocytes (emperipolesis).
91FF17.jpg|Fig. 91.17 Xanthoma disseminatum. Flexural involve
ment is common. In this patient, diffuse red–yellow papules are seen in th
e axilla, as well as on the shoulder and proximal arm. Courtesy of Grant J Anhal
t, MD, Johns Hopkins Dermatology
91FF18.jpg|Fig. 91.18 Xanthoma disseminatum. Sclerotic form o
f xanthoma disseminatum in a patient who developed multiple myeloma.
91FT1.jpg|Table 91.1 Clinical features of the histiocytoses.
91FT2.jpg|Table 91.2 Antigenic markers of the histiocytoses.
92FF1.jpg|Fig. 92.1 Eruptive xanthomas of the extensor surfaces o
f the lower extremities. This patient had marked hypertriglyceridemia.
92FF2.jpg|Fig. 92.2 Eruptive xanthomas. Note the yellowish hu
e and ‘mulberry’ pattern in a patient with Frederickson type IV dise
ase.
92FF3.jpg|Fig. 92.3 Underlying disorders in eruptive xanthomas. Courtesy of Yale Residents Slide Collection.
92FF4.jpg|Fig. 92.4 Tuberoeruptive xanthomas of the elbow. No
te the yellowish hue.
92FF5.jpg|Fig. 92.5 Nodular tuberous xanthomas of the elbows.
This form occurred in a young patient with familial hypercholesterolemia.
92FF6.jpg|Fig. 92.6 Tendinous xanthoma. Linear swelling of th
e Achilles area representing a tendinous xanthoma in a patient with dysbetalipop
roteinemia.
92FF7.jpg|Fig. 92.7 Tendinous xanthomas of the fingers in a patie
nt with homozygous familial hypercholesterolemia. Note intertriginous plane
xanthomas of the web spaces.
92FF8.jpg|Fig. 92.8 Plane xanthomas of the antecubital fossae in
a young patient with homozygous familial hypercholesterolemia.
92FF9.jpg|Fig. 92.9 Plane xanthomas of the palmar creases in a pa
tient with dysbetalipoprotenemia (arrows).
92FF10.jpg|Fig. 92.10 Xanthelasma palpebrarum with typical yellow
ish hue. Courtesy of Yale Residents Slide Collection.
92FF11.jpg|Fig. 92.11 Plane xanthoma in a patient with a monoclon
al IgG gammopathy.
92FF12.jpg|Fig. 92.12 Xanthoma. Foamy macrophages (histiocyte
s) in the dermis. Courtesy Ron Rapini, M.D.
92FF13.jpg|Fig. 92.13 Tuberous xanthoma. Scanning view of fib
rosis with foamy macrophages and cholesterol clefts. Courtesy Ron Rapini, M.D.
92FF14.jpg|Fig. 92.14 Histologic section of a plane xanthoma demo
nstrating multiple foam cells.
92FT1.jpg|Table 92.1 Important apoproteins.
92FT2.jpg|Table 92.2 Important hyperlipoproteinemias. LDL, lo
w-density lipoproteins; VLDL, very low-density lipoproteins; LPL, lipoprotein li
pase.
92FT3.jpg|Table 92.3 Differential diagnosis of xanthomas.
93FF1.jpg|Fig. 93.1 Non-infectious granulomas. Paradigm for h
istologic diagnosis.
93FF2.jpg|Fig. 93.2 Sarcoidosis. A Cutaneous sarcoidosis usua
lly consists of papules and plaques with a typical reddish-brown color. B
Lesions often favor the lips and perioral region. C An ichthyosiform pre
sentation is less common. C, courtesy of Jean Bolognia, M.D.
93FF3.jpg|Fig. 93.3 Sarcoidosis. With diascopy, an ‘app
le jelly’ color is seen.
93FF4.jpg|Fig. 93.4 Sarcoidosis. A Scanning power of cutaneou
s sarcoidosis demonstrating nodular aggregates of epithelioid histiocytes formin
g tubercles filling the dermis and extending into the subcutaneous tissue. B Higher power of a sarcoidal tubercle with a sparse admixture of lymphocytes
(‘naked tubercle’).
93FF5.jpg|Fig. 93.5 Sarcoidosis. High magnification demonstra
ting an asteroid body within the cytoplasm of a multinucleated epithelioid histi
ocyte in cutaneous sarcoidosis.
93FF6.jpg|Fig. 93.6 Granuloma annulare. Clinical appearance o
f granuloma annulare consisting of papules coalescing into an arciform plaque on
the dorsum of the hand (A) and the extensor arm (B). Note the red-brown color o
f previously involved skin.
93FF7.jpg|Fig. 93.7 Disseminated granuloma annulare. Numerous
papules and annular plaques.
93FF8.jpg|Fig. 93.8 Perforating granuloma annulare. Some papu
les have a keratotic plug. Courtesy of Ron Rapini, M.D.
93FF9.jpg|Fig. 93.9 Granuloma annulare. GA at scanning magnif
ication demonstrating epithelioid histiocytes forming a nodule in the upper derm
is. The histiocytes are arranged in palisaded fashion with adjacent more darkly
staining perivascular lymphocytes.
93FF10.jpg|Fig. 93.10 Granuloma annulare. Higher power of GA
reveals epithelioid histiocytes palisaded around anuclear dermis characterized b
y altered collagen and pallor due to deposition of acid mucopolysaccharide (muci
n).
93FF11.jpg|Fig. 93.11 Papular granuloma annulare of the elbow. The diagnosis can be more difficult when annular plaques are not present. (Cou
rtesy of Ron Rapini, M.D.)
93FF12.jpg|Fig. 93.12 Necrobiosis lipoidica. Note the orangeyellow atrophic plaques on the shin.
93FF13.jpg|Fig. 93.13 Necrobiosis lipoidica. A Biopsy of necr
obiosis lipoidica reveals epithelioid histiocytes, some of them multinucleated,
arranged in palisaded fashion throughout the dermis and extending into subcutane
ous fat septae. B Higher power of necrobiosis lipoidica reveals altered c
ollagen surrounded by palisaded histiocytes.
93FF14.jpg|Fig. 93.14 Annular elastolytic giant cell granuloma (a
ctinic granuloma). The border resembles granuloma annulare but the central p
ortion is hypopigmented and atrophic.
93FF15.jpg|Fig. 93.15 Actinic granuloma. Loss of elastic fibr
es (black) is seen amid the granulomatous infiltrate (yellow). The remaining col
lagen is stained red. Courtesy of Ron Rapini, M.D.
93FT1.jpg|Table 93.1 Clinical features of the major granulomatous
dermatitides. AEGCG, annular elastolytic giant cell granuloma; GA, granulom
a annulare; NLD, necrobiosis lipoidica diabeticorum. *Clinical variants include
generalized, micropapular, nodular, perforating, subcutaneous, and patch GA.
93FT2.jpg|Table 93.2 Histologic features of the major granulomato
us dermatitides. AEGCG, annular elastolytic giant cell granuloma; GA, granul
oma annulare; NLD, necrobiosis lipoidica diabeticorum.
93FT3.jpg|Table 93.3 Treatment of cutaneous sarcoidosis. 1, D
ouble-blind study; 2, case series; 3, anecdotal.
93FT4.jpg|Table 93.4 Treatment of granuloma annulare. 1, Doub
le-blind study; 2, case series; 3, anecdotal.
94FF1.jpg|Fig. 94.1 Granulomatous reaction to collagen injection.
 Courtesy of Yale Residents Slide Collection.
94FF2.jpg|Fig. 94.2 Birefringent foreign body is engulfed by a fo
reign body type giant cell with the typical haphazard array of nuclei. Court
esy of Tom Horn, M.D.
94FF3.jpg|Fig. 94.3 An approach to the patient with suspected for
eign body reaction.
94FF4.jpg|Fig. 94.4 Wood splinter in the dermis, surrounded by gr
anulomatous inflammation. Courtesy of Ron Rapini, MD.
94FF5.jpg|Fig. 94.5 Traumatic tattoo of the chin. Bluish disc
oloration and erythema, predominantly due to silica foreign body. Courtesy of Ro
n Rapini, MD.
94FF6.jpg|Fig. 94.6 Granulomas due to allergic reaction to the re
d (cinnabar) portions of a tattoo. Courtesy of Ron Rapini, MD.
94FF7.jpg|Fig. 94.7 Coral envenomation. Delayed lichenoid rea
ction on the calf. The patient accidentally contacted a coral reef and developed
acute dermatitis that resolved to be followed three weeks later by this severel
y itchy eruption that responded favorably to intralesional triamcinolone injecti
on.
94FT1.jpg|Table 94.1 Classification of foreign bodies according t
o their origins and routes of entry
94FT2.jpg|Table 94.2 Causes of dermal pigmentation
94FT3.jpg|Table 94.3 Clinical and histopathologic features of for
eign body reactions
95FF1.jpg|Fig. 95.1 Dermal extracellular matrix networks. Dif
ferent molecules polymerize into distinct fibril networks and, within the mesh o
f the networks, cells are embedded in the amorphous extrafibrillar matrix. The f
ibril networks interact with each other, with the extrafibrillar matrix and the
cells. The former have a dual function, i.e. support of the tissue and regulatio
n of cellular functions.
95FF2.jpg|Fig. 95.2 Biosynthesis of a ‘prototype’ col
lagen. The procollagen α-chains are synthesized in the rough endoplasmi
c reticulum. Already during the synthesis of the nascent polypeptide, certain pr
olyl and lysyl residues are hydroxylated and modified by glycosylation. Three &#
945;-chains associate to form a trimer and fold into a triple helix. The newly f
ormed triple helical procollagen is secreted into the extracellular space, where
the N- and C-terminal propeptides are cleaved by specific proteases. The mature
collagen molecules assemble to form mixed fibrils with other collagens and noncollagenous molecules. The suprastructures are stabilized by covalent cross-link
s. (EDS, Ehlers–Danlos syndrome.) Modified from Myllyharju J, Kivirikko KI
. Collagens and collagen-related diseases. Ann Med. 2001;33:7–21.
95FF3.jpg|Fig. 95.3 Supramolecular assemblies of collagens. T
he suprastructures formed by different collagens are shown. Non-collagenous comp
onents also interact with the fibrils and networks. The suprastructural organiza
tion of the transmembrane collagens XIII and XVII and the multiplexin collagens
XV and XVIII is not known yet (panels 7 and 8). These collagens are in close vic
inity to basement membranes and are likely to participate and/or interact with t
he different basement membrane networks. Modified from Myllyharju J, Kivirikko K
I. Collagens and collagen-related diseases. Ann Med. 2001;33:7–21.
95FF4.jpg|Fig. 95.4 Fibrillar and filamentous networks extracted
from human skin. The large cross-banded fibrils represent dermal mixed fibri
ls containing collagens I, III, V, other minor collagens, and decorin. The cross
-banding has a characteristic periodicity of 64 nm. The filamentous network
in the background contains microfibrillar and basement membrane components. In
this immunoelectron photomicrograph, the black dots are colloidal gold particles
coupled to anti-collagen IV antibodies, indicating that basement membrane netwo
rks are strongly associated with the dermal fibrillar networks. Micrograph kindl
y provided by Dr Uwe Hansen, Dept. Physiological Chemistry, University Hospital
Münster, Germany.
95FF5.jpg|Fig. 95.5 Microfibrils in the papillary dermis. Con
focal scanning microscopy of microfibrils which emerge from the epidermis and tr
averse the papillary dermis perpendicularly. The immunostaining is with antibodi
es to fibrillin 1 (red) and latent TGF-β complex (green). The orange–
yellow color demonstrates co-localization of both proteins on the microfibrils.
Note that the epidermal keratinocytes contain latent TGF-β. The micrograph
is kindly provided by Dr Michael Raghunath, University of Münster, Mün
ster, Germany. See also Raghunath et al. 199821.
95FF6.jpg|Fig. 95.6 Versican structure and aggregates. A The
core protein contains several structural motifs important for GAG and ligand bin
ding. The N-terminal immunoglobulin-type repeat (Ig) is followed by two consecut
ive link-protein type modules (LP), which are involved in mediating the binding
of the core protein to hyaluronic acid. The GAG binding domain, which comes in t
issue-specific alternative splice variants, GAG-α and/or GAG-β, carrie
s the GAG side chains. It is followed by structural motifs including two EGF-lik
e repeats (EG), a C-type lectin domain (Lectin), and a complement regulatory pro
tein-like module (CR). B In the dermis versican can form huge aggregates
with hyaluronic acid (red). The core protein (blue), which carries a number of G
AG side chains (black), is bound to hyaluronic acid via its link-protein domain
(green; LP module in the scheme in panel A). The aggregates can bind large amoun
ts of water, and thus provide for the tautness of the skin. Modified from Iozzo
RV. Matrix proteoglycans: from molecular design to cellular function. Ann Rev Bi
ochem. 1998;67:609–52.
95FF7.jpg|Fig. 95.7 Phenotypic manifestations of genetic extracel
lular matrix defects. A Ehlers–Danlos syndrome type II with slightly o
verstretchable skin results from mutations in the collagen V genes. B Aut
osomal dominant cutis laxa is associated with mutations in the elastin gene. 
C Pseudoxanthoma elasticum with yellowish lax skin due to mutations in the ABCC6 transporter gene. D Junctional epidermolysis bullosa with ski
n blisters after minimal friction is caused by mutations in the collagen XVII ge
ne.
95FT1.jpg|Table 95.1 Components of the extracellular matrix (ECM)
. The dermal ECM components belong to several protein superfamilies. The mol
ecules assemble into mixed fibrils and networks in a tissue-specific manner. Sev
eral enzymes are involved in the biosynthesis and modification of ECM assemblies
. Integrins are the main cellular receptors for the ECM *LTBP, latent TGF-β
-binding protein.
95FT2.jpg|Table 95.2 The collagen family of proteins. ECM, ex
tracellular matrix; FACITs, fibril-associated collagens with interrupted triple
helices.
95FT3.jpg|Table 95.3 Proteoglycans of the skin. *Small leucin
e-rich proteoglycan.
95FT4.jpg|Table 95.4 Glycoproteins of the skin.
95FT5.jpg|Table 95.5 Genetic extracellular matrix diseases of the
skin. ADAM, a disintegrin and metalloproteinase.
95FT6.jpg|Table 95.6 Extracellular matrix components as targets i
n autoimmune diseases *Tan et al. described anti-fibrillin antibodies in Cho
ctaw Native Americans with the highest prevalence of scleroderma yet described (
J Immunol. 1999;163:1066–72). In a later study, the same authors reported
striking racial differences in antigenic epitope specificity of anti-fibrillin 1
antibodies in scleroderma patients from different populations (Arthritis Rheum.
2000;43:2464–71).
96FF1.jpg|Fig. 96.1 Keratotic papule of reactive proliferating co
llagenosis on the upper extremity. This followed minor trauma in a healthy m
an who had developed similar papules since childhood.
96FF2.jpg|Fig. 96.2 Multiple annular plaques of EPS composed of k
eratotic papules on the arm of a patient receiving penicillamine.
96FF3.jpg|Fig. 96.3 Keratotic papules of EPS arranged in an annul
ar configuration on the anterior neck of a woman receiving penicillamine.
96FF4.jpg|Fig. 96.4 In the axilla, annular plaques of EPS and the
changes of PXE (redundant skinfolds, yellow discoloration).
96FF5.jpg|Fig. 96.5 Keratotic papules of acquired perforating der
matosis on the arm of a diabetic woman on hemodialysis. Note the central ker
atotic core which is sometimes dislodged by the patient.
96FF6.jpg|Fig. 96.6 Koebner phenomenon in acquired perforating de
rmatosis. The biopsy specimen demonstrated transepidermal elimination of col
lagen.
96FF7.jpg|Fig. 96.7 Perforating periumbilical calcific elastosis
in a multiparous African–American woman. When a biopsy is performed of
the elevated edge, resistance is felt as well as a grinding sound.
96FF8.jpg|Fig. 96.8 Scanning view of crusted keratotic plug in th
e reactive perforating collagenosis type of acquired perforating dermatosis
(hematoxylin and eosin stain).

96FF9.jpg|Fig. 96.9 Higher power view of collagen fibers extendin
g through the epidermis (arrows) into the crusted plug in reactive perforating c
ollagenosis (hematoxylin and eosin stain).
96FF10.jpg|Fig. 96.10 Transepidermal elimination of red collagen
fibers through the spinous layer and into the stratum corneum in reactive perfor
ating collagenosis (Verhoeff–van Gieson stain).
96FF11.jpg|Fig. 96.11 Elastosis perforans serpiginosa. Hyperp
lastic epidermis clutches the increased dermal elastic fibers like a claw (hemat
oxylin and eosin stain).
96FF12.jpg|Fig. 96.12 Elastosis perforans serpiginosa. Transe
pidermal elimination of neutrophils and elastic fibers from the dermis through a
channel in the epidermis (hematoxylin and eosin stain).
96FF13.jpg|Fig. 96.13 Approach to the patient with a primary perf
orating disease.
96FT1.jpg|Table 96.1 Major perforating diseases. EPS, elastos
is perforans serpiginosa; RPC, reactive perforating collagenosis.
96FT2.jpg|Table 96.2 Secondary perforating diseases.
96FT3.jpg|Table 96.3 Differential diagnosis of perforating diseas
es.
96FT4.jpg|Table 96.4 Treatment of perforating diseases. Key t
o evidence-based support: double-blind studies; clinical series; anecdotal evide
nce.
97FF1.jpg|Fig. 97.1 Pathogenesis of sclerosis. Three componen
ts are involved during the formation of sclerosis: vascular damage, lymphocyte a
ctivation and altered connective tissue production.
97FF2.jpg|Fig. 97.2 Animal model for scleroderma. Transfer of
scleroderma phenotypes from diseased animals (TSK mice) to healthy syngeneic mi
ce by bone marrow cells.
97FF3.jpg|Fig. 97.3 Early inflammatory plaque type morphea of the
trunk. Early stage lesion presented by violaceous, edema-like plaque.
97FF4.jpg|Fig. 97.4 Plaque-type morphea of the trunk. Between
the two large hyperpigmented plaques is a shiny white sclerotic plaque with a l
ilac border. Courtesy of Yale Residents Slide Collection.
97FF5.jpg|Fig. 97.5 Comparison of deep morphea and eosinophilic f
asciitis. A Note the ‘pseudo-cellulite’ appearance of the involv
ed skin of the thigh in deep morphea. B In eosinophilic fasciitis, the le
vel of fibrosis is also deep.
97FF6.jpg|Fig. 97.6 Parry–Romberg syndrome. Hyperpigmen
tation and loss of subcutaneous tissue is seen, leading to facial asymmetry. Cou
rtesy of Ron Rapini, MD.
97FF7.jpg|Fig. 97.7 Linear morphea of the leg.
97FF8.jpg|Fig. 97.8 Morphea en coup de sabre. Note the obviou
s linear depressions.
97FF9.jpg|Fig. 97.9 Linear morphea of the leg in a child. Uni
lateral hypotrophy as a result of untreated disabling morphea.
97FF10.jpg|Fig. 97.10 Histology of scleroderma. Overview (lef
t), infiltrating cells surrounding small vessels (middle), advanced sclerosis of
the entire dermis (right).
97FF11.jpg|Fig. 97.11 Lichen sclerosus of the neck. Papules a
nd small plaques (A) versus large plaque (B).
97FF12.jpg|Fig. 97.12 Lichen sclerosus. Follicular plugging i
n a plaque of LS on the back in a patient with chronic graft-versus-host disease
(A). Hemorrhagic bullae on the leg (B). A Courtesy of Jean
Bolognia, M.D. B Courtesy of Yale Residents Slide Collection.
97FF13.jpg|Fig. 97.13 Vulvar lichen sclerosus. Centrally ther
e is erythema with superficial erosion and purpura. More peripherally, white pla
ques with a wrinkled surface are seen.
97FF14.jpg|Fig. 97.14 Lichen sclerosus on the glans. Also kno
wn as balanitis xerotica obliterans, this is a common cause of phimosis.
97FF15.jpg|Fig. 97.15 Histology of lichen sclerosus. Homogeni

zed papillary dermis with lymphocytic infiltrate beneath that zone is classic. A
flattened dermo-epidermal junction is also seen.
97FF16.jpg|Fig. 97.16 Phototherapy of morphea. Disseminated m
orphea on the trunk before (A) and after phototherapy (B).
97FF17.jpg|Fig. 97.17 High-frequency ultrasound (20 MHz) of a mor
phea plaque. Before (A) and after (B) phototherapy showing red
uction of corium thickness and hyperechoic bands of connective tissue.
97FF18.jpg|Fig. 97.18 Ultrapotent topical corticosteroids in the
treatment of lichen sclerosus. Before (A) and after topical applicati
on of clobetasol propionate 0.05% cream (B).
97FT1.jpg|Table 97.1 Treatment of morphea and lichen sclerosus. +++ Highly effective; ++,effective +, moderately effective; 0, low efficacy o
r ineffective. 1, double-blind controlled trials; 2, clinical trial; 3, anecdota
l report.
98FF1.jpg|Fig. 98.1 Collagen biosynthesis, secretion and fibril a
ssembly, and identification of pathological mechanisms leading to EDS phenotype.
 Glc-Gal, glucosyl-galactosyl residue attached to the hydroxyl group (OH) of
lysine residues; S-S bonds, disulfide bonds; AD, autosomal dominant; AR, autoso
mal recessive; IC, intracellular; EC, extracellular. The pathomechanism of the h
ypermobility subtype (see Table 98.1) is not known.
98FF2.jpg|Fig. 98.2 Clinical features of Ehlers–Danlos synd
rome. Patients with classical EDS demonstrating joint hypermobility (A), hyperextensibile skin (B), a widened atrophic scar (C), mollus
coid pseudotumors (D) and Gorlin's sign (E).
98FF3.jpg|Fig. 98.3 Approach to the patient with Ehlers–Dan
los syndrome. See also Table 98.1. Courtesy of Yale Residents Slide Collecti
on.
98FF4.jpg|Fig. 98.4 Clinical features of pseudoxanthoma elasticum
. A Yellowish papules on the lateral neck sparing the posterior midline. 
B Plaques of yellowish papules and loose skin on the lateral neck of a 22-ye
ar-old woman. C Firm, calcified plaques within long-standing skin lesions
. D Sagging skin in the axilla. E Yellowish papules on the shoulde
r in the setting of generalized skin involvement.
98FF5.jpg|Fig. 98.5 Mucosal lesions in pseudoxanthoma elasticum.
98FF6.jpg|Fig. 98.6 Angioid streaks in pseudoxanthoma elasticum (
arrow).
98FF7.jpg|Fig. 98.7 Histopathology of pseudoxanthoma elasticum. A
 Purple clumps in the mid and deep reticular dermis in H&E-stained secti
ons represent calcium deposits on elastic fibers in advanced PXE. B Verho
eff van Giesson elastic stain reveals black-staining, irregularly clumped elasti
c fibers.
98FF8.jpg|Fig. 98.8 Clinical features in cutis laxa. A Loose
and sagging skin in a newborn, B a sagging jowl of a 4-year old boy, and
C prematurely aged appearance of a 30-year-old patient. Modified with per
mission from Uitto J, Pulkkinen L. Heritable disorders affecting the elastic tis
sues: cutis laxa, pseudoxanthoma elasticum and related disorders. In: Rimoin DL,
Connor JM, Pyeritz RE (eds). Emery and Rimoin's Principles and Practice of Medi
cal Genetics, 3rd edn. London: Churchill Livingstone, 2002.
98FF9.jpg|Fig. 98.9 Clinical features in cutis laxa. A Premat
ure aging appearance of a 15-year-old patient with CL. B Chest radiograph
demonstrates severe pulmonary emphysema. C Histopathology of the skin de
picts fragmentation of dermal elastic fibers. Modified with permission from Uitt
o J, Pulkkinen L. Heritable disorders affecting the elastic tissues: cutis laxa,
pseudoxanthoma elasticum and related disorders. In: Rimoin DL, Connor JM, Pyeri
tz RE (eds). Emery and Rimoin's Principles and Practice of Medical Genetics, 3rd
edn. London: Churchill Livingstone, 2002.
98FT1.jpg|Table 98.1 Classification of Ehlers–Danlos syndro
me. *According to The 1997 Villefranche Consensus Meeting5. 
+This classification has been replaced by ref. 5. ‡The pr

evious EDS type IX has been reclassified as occipital horn syndrome, a disorder
allelic with Menkes syndrome (see Chapter 63). †The classical f
orms due to type V collagen mutations are inherited in an autosomal dominant (AD
) fashion, while those caused by tenascin-X deficiency are autosomal recessive (
AR) (see Fig. 98.1).
98FT2.jpg|Table 98.2 Comparison of selected clinical features in
EDS and Marfan syndrome.
98FT3.jpg|Table 98.3 Acquired cutis laxa: clinical presentations
and associated conditions
99FF1.jpg|Fig. 99.1 Pathogenesis of hypertrophic scars in keloids
.
99FF2.jpg|Fig. 99.2 Hypertrophic scars. A A 5-month old scar
that is still pink. B A 1-year old scar that is hypopigmented. Courtesy o
f Jean Bolognia, M.D.
99FF3.jpg|Fig. 99.3 Spontaneous generalized keloids. Extensiv
e spontaneous keloids in a patient with darkly pigmented (A) and a patien
t with lightly pigmented (B) skin.
99FF4.jpg|Fig. 99.4 Acne-induced keloids.
99FF5.jpg|Fig. 99.5 Hypertrophic scarring following an episode of
herpes zoster. Elevated scars are limited to the area of infection.
99FF6.jpg|Fig. 99.6 Keloid scarring. Note the extension of th
e keloid scar into the normal tissue and the central involution.
99FF7.jpg|Fig. 99.7 Histopathology of a hypertrophic scar and a k
eloid. A Hypertrophic scar. B Keloids. C Keloids close-up. Cou
rtesy of Thomas Cummings, M.D.
99FF8.jpg|Fig. 99.8 Flashlamp-pumped pulsed-dye laser treatment.
A Hypertrophic scar before and B after treatment with a flashlamp-pum
ped pulsed-dye laser.
99FF9.jpg|Fig. 99.9 Knuckle pads. Fibromatous thickening of d
igital skin overlying the joints.
99FF10.jpg|Fig. 99.10 Dupuytren's contracture. A fibrotic cor
d (arrow) can be felt and accentuated by extension of the digits.
99FT1.jpg|Table 99.1 Differences in adult versus fetal wound heal
ing24.
99FT2.jpg|Table 99.2 Key features of normal, hypertrophic and kel
oid scars.
99FT3.jpg|Table 99.3 Treatment options for hypertrophic scars and
keloids. *1, Double-blind study; 2, case series; 3, anecdotal. **As a compo
nent of combined therapy-K, keloids; HS, hypertrophic scar.
100FF1.jpg|Fig. 100.1 Mid-dermal elastolysis. Well-circumscri
bed area of fine wrinkling on the neck of a middle-aged woman. Courtesy of Richa
rd Dubuc, M.D.
100FF2.jpg|Fig. 100.2 Histology of mid-dermal elastolysis. No
te selective loss of elastic fibers in the mid-dermis. Normal elastic tissue is
preserved in the superficial papillary dermis and in the reticular dermis (Weige
rt's stain). Courtesy of Danielle Bouffard, M.D.
100FF3.jpg|Fig. 100.3 Anetoderma. A Small, flaccid sac-like p
rotrusion on the back; note the central depression. B Circumscribed aneto
derma, secondary to cutaneous sarcoidosis. C Soft sac-like protrusion. C, Courtesy of Ron Rapini, M.D.
100FF4.jpg|Fig. 100.4 Anetoderma. Pathology shows decrease of
elastic fibers in the papillary and reticular dermis (Weigert's stain).
100FF5.jpg|Fig. 100.5 Striae. A Linear erythematous lesions o
n the abdomen (striae rubra). B Atrophic linear lesions of striae alba in
a teenager. B, Courtesy of Kalman Watsky, M.D.
100FF6.jpg|Fig. 100.6 Atrophoderma of Pasini and Pierini. A M
ultiple depressed, slightly hyperpigmented patches on the back. B Coalesc
ent hyperpigmented patches on the abdomen. A Courtesy of Catherine C McCuaig, M.
D.
100FF7.jpg|Fig. 100.7 Atrophoderma vermiculatum. Multiple sma

ll pitted scars on the cheek of a young girl. Note the honeycomb pattern on the
lower inner cheek. Courtesy of Robert Hartman, M.D.
100FF8.jpg|Fig. 100.8 Atrophia maculosa varioliformis cutis.
Small round atrophic scar-like lesions progressing over the previous two years.
There was no associated keratosis pilaris and no history of trauma or inflammati
on.
100FF9.jpg|Fig. 100.9 Piezogenic pedal papules. Skin-colored
papules on the sides of the heel in the weight-bearing position. These represent
small fat herniations.
100FT1.jpg|Table 100.1 Disorders of elastic tissue.
100FT2.jpg|Table 100.2 Classification of anetoderma.
100FT3.jpg|Table 100.3 Secondary anetoderma – associated co
nditions.
101FF1.jpg|Fig. 101.1 Most common locations for several forms of
panniculitis. The categories for classification of panniculitis are determin
ed partly by clinical characteristics such as location, partly by histopathology
, and partly by etiology.
101FF2.jpg|Fig. 101.2 Erythema nodosum. Erythematous nodules
located bilaterally on the lower legs. Photograph courtesy Kenneth E. Greer, MD.
101FF3.jpg|Fig. 101.3 Erythema nodosum. Septa are widened and
edematous, and infiltrated by lymphocytes and neutrophils.
101FF4.jpg|Fig. 101.4 Erythema nodosum. Miescher's microgranu
lomas within septa.
101FF5.jpg|Fig. 101.5 Morphea panniculitis. Septal thickening
, mucin deposition, and mild lymphocytic infiltration.
101FF6.jpg|Fig. 101.6 Alpha1-antitrypsin deficiency pa
nniculitis. Purpuric nodules on the ankle. Photograph courtesy Kenneth E. Gr
eer, MD.
101FF7.jpg|Fig. 101.7 Erythema induratum. Nodular lesions on
lower leg with evidence of ulceration. Photograph courtesy Kenneth E. Greer, MD.
101FF8.jpg|Fig. 101.8 Erythema induratum. Vasculitis involvin
g a medium-sized vessel in the subcutis.
101FF9.jpg|Fig. 101.9 Erythema induratum. Zone of caseous nec
rosis surrounded by a palisade of macrophages and multinucleated giant cells.
101FF10.jpg|Fig. 101.10 Pancreatic panniculitis. Nodules on t
he legs. Photograph courtesy Kenneth E. Greer, MD.
101FF11.jpg|Fig. 101.11 Pancreatic panniculitis. Neutrophilic
inflammation, cellular necrosis, and deposition of homogeneous basophilic mater
ial due to saponification of fat by calcium salts.
101FF12.jpg|Fig. 101.12 Sclerema neonatorum. Needle-shaped cl
efts within lipocytes, in the absence of inflammation.
101FF13.jpg|Fig. 101.13 Subcutaneous fat necrosis of the newborn. Indurated plaques on the trunk.
101FF14.jpg|Fig. 101.14 Subcutaneous fat necrosis of the newborn. Needle-shaped clefts in radial configuration are present within giant cells
.
101FF15.jpg|Fig. 101.15 Lupus panniculitis. This patient actu
ally had a lupus erythematosus-dermatomyositis overlap syndrome. Photograph cour
tesy Kenneth E. Greer, MD.
101FF16.jpg|Fig. 101.16 Lupus panniculitis. Nodular aggregate
of lymphocytes in the subcutis, with lymphoid follicle configuration.
101FF17.jpg|Fig. 101.17 Cold panniculitis. Erythematous, viol
aceous plaques on the thighs in a case of equestrian cold panniculitis. Photogra
ph courtesy Kenneth E. Greer, MD.
101FF18.jpg|Fig. 101.18 Oil granuloma. Numerous vacuolated sp
aces, in this case due to grease gun injury.
101FF19.jpg|Fig. 101.19 Lipodermatosclerosis. Sclerotic plaqu
e on the lower leg. Photograph courtesy Kenneth E. Greer, MD.
101FF20.jpg|Fig. 101.20 Lipodermatosclerosis. Lipomembranous
change, consisting of cystic formation with elaborate papillary configurations.

101FF21.jpg|Fig. 101.21 Infection-induced panniculitis. Bacte
rial panniculitis, showing heavy neutrophilic inflammation, basophilic necrosis,
vascular proliferation, and hemorrhage.
101FF22.jpg|Fig. 101.22 Cytophagic histiocytic panniculitis.
Subcutaneous nodules with purpura. Photograph courtesy Kenneth E. Greer, MD.
101FF23.jpg|Fig. 101.23 Cytophagic histiocytic panniculitis.
Macrophages engaged in cytophagic activity. Some of them have the appearance of
‘bean bag cells’.
101FT1.jpg|Table 101.1 Classification of the panniculitides
101FT2.jpg|Table 101.2 An approach to the histopathologic diagnos
is of panniculitis.
101FT3.jpg|Table 101.3 Causes of erythema nodosum
101FT4.jpg|Table 101.4 Findings suggestive of a systemic cause fo
r erythema nodosum
102FF1.jpg|Fig. 102.1 Lipodystrophy syndromes.
102FF2.jpg|Fig. 102.2 Proposed pathogenesis of protease inhibitor
-induced lipodystrophy syndrome. Adipocyte apoptosis and abnormal differenti
ation occur via reduced retinoid X receptor (RXR) activation. This may occur via
(1) direct homologous binding to cytoplasmic retinoic acid binding protein type
1 (CRABP-1), preventing conversion of RA to cis-9-retinoic acid or (2) i
nhibition of P450 isoforms needed to metabolize retinoic acid (RA) to cis
-9-retinoic acid. Lipids, now unable to be stored in fat, are released. Low-dens
ity receptor-related protein (LRP) present on capillary endothelium in a complex
with lipoprotein lipase (LPL) and in the liver, may also be inhibited, resultin
g in reduced cleavage of fatty acids from circulating triglycerides (3) and decr
eased hepatic uptake of chylomicrons (4), respectively. The cascade of metabolic
events from increased circulating triglycerides includes fat redistribution, wi
th increased storage of fat in the abdomen, breast, and dorsocervical region, hy
perlipidemia, and insulin resistance. Adapted from Carr A. HIV protease inhibito
r-related lipodystrophy syndrome. Clin Infect Disease. 2000;30:S135–42.
102FF3.jpg|Fig. 102.3 Congenital generalized lipodystrophy syndro
me in a patient with a strong family history. A Extensive acanthosis nigrica
ns, facial and extremity lipodystrophy, and muscular habitus. B Close up
view demonstrating loss of Bichat's fat pad and buccal fat. Courtesy of Kenneth
E Greer, M.D., University of Virginia.
102FF4.jpg|Fig. 102.4 A child with acquired generalized lipodystr
ophy and thyroiditis. A There is prominent lower extremity lipodystrophy, wi
th muscular features and prominent veins. B The buttock is involved. Cour
tesy of Julie Allee, M.D.
102FF5.jpg|Fig. 102.5 Lipoatrophy, demonstrating involvement of t
he limbs with muscular features. Courtesy of William D James, M.D., Universi
ty of Pennsylvania.
102FF6.jpg|Fig. 102.6 Acquired partial lipodystrophy syndrome in
a patient with nephritic factor and renal disease. A Lipoatrophic features a
re most prominent on the face. B Closer view demonstrating marked loss of
buccal fat. Axillary acanthosis nigricans is present. Courtesy of Kenneth E Gre
er, M.D., University of Virginia.
102FF7.jpg|Fig. 102.7 Patient with localized lipoatrophy of the t
high associated with subcutaneous panniculitis-like T cell lymphoma.
102FF8.jpg|Fig. 102.8 Insulin-related lipodystrophy. Courtesy
of Ron Rapini, M.D.
102FF9.jpg|Fig. 102.9 Skin biopsy from a child with acquired gene
ralized lipodystrophy demonstrating pre-atrophic inflammatory changes. A Sca
nning power demonstrates a lobular panniculitis. B High power reveals the
panniculitis to be composed of lymphocytes, histiocytes, multinucleated giant c
ells, lipophages, and phagocytized mucopolysaccaride. There is microcystic alter
ation of fat cells.
102FF10.jpg|Fig. 102.10 Skin biopsy of involutional lipoatrophy s
econdary to injected corticosteroid. A There is marked diminution and collap
se of the fat lobule, without inflammation. B Higher power demonstrates d

ecreased size of fat cells with eosinophilic thickened cell walls with a hyalini
zed and mucinous stroma.
102FT1.jpg|Table 102.1 Lipodystrophy syndromes. AR, autosomal
recessive; AD, autosomal dominant; IR, insulin resistance; DM, diabetes mellitu
s; TG, triglycerides; chol, cholesterol; chrom, chromosome; PI, protease inhibit
or; MCGNIII, mesangiocapillary glomerulonephritis III; C3NeF, C3 nephritic facto
r; HIV, human immunodeficiency virus.
102FT2.jpg|Table 102.2 Features of generalized congenital lipodys
trophy6,29. TG, triglyceride; HDL, high density lipoprotein.
103FF1.jpg|Fig. 103.1 Outline of the cutaneous vascular system. The superficial vascular plexus feeds vessels in the dermal papillae; arterie
s (red) and veins (blue) are closely associated with lymphatic vessels (yellow).
103FF2.jpg|Fig. 103.2 Intravascular perfusion with the lectin
Leucopersicon esculentum. This procedure reveals dense irregular vascula
r networks in murine skin and is usually visualized by whole-mount preparation o
f ear skin.
103FF3.jpg|Fig. 103.3 Distinct immunofluorescent staining of cuta
neous blood vessels (PAL-E; green) and lymphatic vessels (LYVE-1; red) in human
neonatal foreskin. The dotted line indicates the basement membrane zone.
103FF4.jpg|Fig. 103.4 Blood supply of the hair follicle. A si
ngle vascular loop extends into the dermal papilla of the hair follicle (CD31)
103FF5.jpg|Fig. 103.5 Ultrastructural visualization of a rod-shap
ed Weibel–Palade body (WPB) within the cytoplasm of a human endothelial ce
ll.
103FF6.jpg|Fig. 103.6 Consecutive steps of vasculogenesis and ear
ly angiogenesis during embryogenesis. The schematic includes the formation a
nd remodeling of primordial vascular networks. FGFR, fibroblast growth factor re
ceptor; FGF, fibroblast growth factor; VEGF, vascular endothelial growth factor;
VEGFR, vascular endothelial growth factor receptor; Ang-1, angiopoietin-1; TGF,
transforming growth factor; PDGF, platelet-derived growth factor.
103FF7.jpg|Fig. 103.7 Angiopoietins play an important role in the
interactions between endothelial cells and pericytes in quiescent and in angiog
enic vessels. Upregulation of angiopoietin-2 (Ang-2) in angiogenic endotheli
al cells (EC) blocks the vessel-stabilizing effect of pericyte (PC)-derived angi
opoietin-1 (Ang-1) via the endothelial Tie-2 receptor.
103FF8.jpg|Fig. 103.8 Molecular control of skin angiogenesis by V
EGF and PlGF. Expression of VEGF and PlGF by keratinocytes is upregulated in
psoriasis, healing wounds and cutaneous squamous cell carcinomas.
103FF9.jpg|Fig. 103.9 The thrombospondin family of matricellular
proteins. TSP-1 and TSP-2 are potent endogenous inhibitors of skin angiogene
sis.
103FF10.jpg|Fig. 103.10 The multistep process of leukocyte–
endothelial cell interactions that leads to leukocyte recruitment into inflamed
skin.
103FF11.jpg|Fig. 103.11 Adhesion molecules of the selectin and im
munoglobulin families.
103FF12.jpg|Fig. 103.12 Schematic representation of the mechanism
s involved in fluid drainage via cutaneous lymphatic vessels. A Normal skin;
B Edema due to blood vascular hyperpermeability.
103FF13.jpg|Fig. 103.13 Embryonic development of the lymphatic va
scular system.
103FF14.jpg|Fig. 103.14 Double-immunofluorescence stain for the l
ymphatic marker LYVE-1 (green) and the basement membrane component laminin (red)
reveals basement membranes (red) and lymphatic vessels (green; arrows).
103FF15.jpg|Fig. 103.15 Specific immunofluorescent staining of CD
31-positive blood vessels (green) that are LYVE-1 negative and of CD31-negative/
LYVE-1-positive lymphatic vessels (red) in human foreskin. Nuclei are staine
d blue.
103FF16.jpg|Fig. 103.16 Vascular endothelial growth factors and t
heir receptors involved in angiogenesis and lymphangiogenesis.

103FT1.jpg|Table 103.1 The stepwise induction of angiogenesis.
103FT2.jpg|Table 103.2 Major adhesion molecules involved in leuko
cyte–endothelial cell interactions: cell-type specific expression, ligands
and function.
103FT3.jpg|Table 103.3 Differential expression of vascular marker
s in cutaneous versus lymphatic vessels.
104FF1.jpg|Fig. 104.1 Hemangioma precursor. The lesion has a
‘bruised’ appearance.
104FF2.jpg|Fig. 104.2 Superficial hemangioma mimicking a capillar
y malformation.
104FF3.jpg|Fig. 104.3 Superficial hemangioma. Note the bright
red color and finely lobulated surface. Courtesy of Ron Rapini, M.D.
104FF4.jpg|Fig. 104.4 Deep hemangiomas. Note the skin-colored
to bluish hue with scattered telangiectasias. A Courtesy of Anthony J Mancini,
M.D.
104FF5.jpg|Fig. 104.5 Hemangioma during involution. Note the
lightening (gray color) and softening of the hemangioma during involution.
104FF6.jpg|Fig. 104.6 Residua of hemangiomas. A, B Minimal hy
popigmentation (arrows) and a circular scar at site of ulceration in the same pa
tient 20 years later; C telangiectasias; and D atrophy and fibrofa
tty changes. A, B, D, Courtesy of Ron Rapini M.D.
104FF7.jpg|Fig. 104.7 Ulcerated hemangiomas. A Ulcerated hema
ngioma in the perineum. B Ulcerated mixed hemangioma on the upper back.
104FF8.jpg|Fig. 104.8 Hemangioma obstructing the visual axis.
This patient also had associated laryngeal involvement requiring a tracheostomy
. Courtesy of Ron Rapini, M.D
104FF9.jpg|Fig. 104.9 Lip hemangioma crossing the vermilion borde
r.
104FF10.jpg|Fig. 104.10 Large Dandy-Walker malformation. This
malformation (arrow) in a patient with a large facial segmental hemangioma, is
characterized by absence of the cerebellar vermis and a large fluid signal inten
sity structure in the posterior fossa.
104FF11.jpg|Fig. 104.11 Anatomical sites of hemangiomas that are
in a ‘beard’ distribution. Involvement of each of the five areas
should be scored as 1 point. In one study of 16 children with a score ≥4,
63% had some degree of symptomatic airway involvement.
104FF12.jpg|Fig. 104.12 Lumbosacral hemangioma associated with te
thered cord. Photograph courtesy of Ilona Frieden, M.D.
104FF13.jpg|Fig. 104.13 Evaluation of an infant hemangioma for po
ssible systemic involvement.
104FF14.jpg|Fig. 104.14 Diffuse neonatal hemangiomatosis. Not
e the multiple small superficial hemangiomas. Courtesy of Ron Rapini, M.D.
104FF15.jpg|Fig. 104.15 Neonatal hemangiomatosis. CT scan dem
onstrating multiple hepatic hemangiomas. Courtesy of Amy Paller, M.D.
104FF16.jpg|Fig. 104.16 Rapidly involuting congenital hemangioma
in a neonate. A Violaceous tumor on the upper extremity. B Spontaneou
s involution at 7 months of age.
104FF17.jpg|Fig. 104.17 Kasabach-Merritt syndrome in a one-week o
ld male. He had a kaposiform hemangioendothelioma. Courtesy of Anthony J Man
cini, M.D.
104FF18.jpg|Fig. 104.18 Proliferating hemangioma. Photomicrog
raph of a proliferating hemangioma with collections of endothelial cells and per
icytes as well as formation of vascular lumens. Courtesy of Ron Rapini, M.D.
104FF19.jpg|Fig. 104.19 Pyogenic granuloma mimicking an infantile
hemangioma. Courtesy Vincent P Beltrani, M.D.
104FF20.jpg|Fig. 104.20 Infantile hemangioma. A An enormous i
nfantile hemangioma of the left cheek, ear and neck despite systemic corticoster
oids (2.5 mg/kg/day for 2–3 months) and complicated by high-output CH
F. B Eleven months after institution of interferon (3 million U/m2/day SC) for 8 months. Courtesy of Richard Antaya, M.D.
104FT1.jpg|Table 104.1 Vascular birthmarks in children.
104FT2.jpg|Table 104.2 Biologic classification of vascular birthm
arks.
104FT3.jpg|Table 104.3 Key features of infantile and congenital h
emangiomas.
104FT4.jpg|Table 104.4 Imaging findings in selected pediatric vas
cular tumors. MRI, magnetic resonance imaging; CT, computed tomography; STM,
soft tissue mass; HFV, high flow vessels; STT, soft tissue thickening; SQ, subc
utaneous. Adapted with permission from Burrows et al. Diagnosic imaging in the e
valuation of vascular birthmarks. Derm Clin. 1998;16:455–8867.
105FF1.jpg|Fig. 105.1 Natural history of hemangiomas and vascular
malformations.
105FF2.jpg|Fig. 105.2 Evaluation of a patient with a presumed cap
illary malformation of the head and neck region. (AVM, arteriovenous malform
ation; CT, computed tomography; CVM, capillary venous malformation; DVA, develop
mental venous anomaly; FPDL, flashlamp-pumped pulsed dye laser; MRA, magnetic re
sonance arteriography; MRI, magnetic resonance imaging; PET, positron emission t
omography; SPECT, single photon emission computed tomography.)
105FF3.jpg|Fig. 105.3 Port-wine stain in a V2 distribution in a y
oung infant. The skin is smooth.
105FF4.jpg|Fig. 105.4 Port-wine stain in V2 distribution in an ad
ult. Hyperplasia and nodularity are prominent.
105FF5.jpg|Fig. 105.5 Port-wine stain in V2 distribution with enl
arged gingiva on the right and overgrowth of the right maxilla.
105FF6.jpg|Fig. 105.6 Capillary malformation (CM) and nevus anemi
cus are intermingled on the shoulder of this man who has phakomatosis pigmentova
scularis type 2b (with Sturge–Weber syndrome).
105FF7.jpg|Fig. 105.7 Lesions of phakomatosis pigmentovascularis
type 2a.
105FF8.jpg|Fig. 105.8 Infant at risk for Sturge–Weber syndr
ome. Port-wine stain: V1 also V1–V3.
105FF9.jpg|Fig. 105.9 Klippel–Trénaunay syndrome.
Geographic capillary stain of the thigh with lymphatic vesicles, dilated incompe
tent veins and enlarged lower limb.
105FF10.jpg|Fig. 105.10 Cutis marmorata telangiectatica congenita
(CMTC) with atrophy of affected limb.
105FF11.jpg|Fig. 105.11 T2-weighted sequence of magnet
ic resonance imaging (MRI) clearly shows venous malformation (VM) in the neck (w
hite hypersignals). The black dots in the white areas of VMs are phleboliths
.
105FF12.jpg|Fig. 105.12 Venous malformation (VM) of cheek and lip
with typical blue color and distortion of facial features with open bite.
105FF13.jpg|Fig. 105.13 Blue lesions of venous malformation (VM)
involving the skin and muscles of an entire arm. Excess slack, blue skin is
prominent in involved fingers, and swelling is obvious in the dependent position
.
105FF14.jpg|Fig. 105.14 Girl with Bean syndrome. Small blue v
enous nodules are superimposed on a large subcutaneous venous malformation. Cour
105FF15.jpg|Fig. 105.15 Plaque-type segmental extremity glomangio
mas. Courtesy of Yale Residents Slide Collection.
105FF16.jpg|Fig. 105.16 Microcystic lymphatic malformation (LM) s
howing a cluster of papulovesicles.
105FF17.jpg|Fig. 105.17 Arteriovenous malformation (AVM) in dorma
nt stage 1, mimicking a port-wine stain. Doppler US confirmed the existing s
hunt.
105FF18.jpg|Fig. 105.18 Arteriovenous malformation (AVM) in expan
sion stage 2. This boy has metameric Bonnet–Dechaume–Blanc syndr
ome (Wyburn–Mason's syndrome) involving the centrofacial skin, the retina

and brain.
105FF19.jpg|Fig. 105.19 Arteriovenous malformation (AVM) in necro
tic stage 3. Shortening of the phalanx and miniaturization of the nail annou
nce the unavoidable amputation of the finger.
105FF20.jpg|Fig. 105.20 Size and locations of ten early small les
ions.
105FF21.jpg|Fig. 105.21 Pathology. A Capillary malformation i
n an adult. Note the increased number of dilated capillaries occupying the whole
dermis. B Venous malformation. Note the large, thin-walled, anastomosing
channels dissecting the normal tissue. C Arteriovenous malformation. The
irregularly thick walled vessels are randomly distributed in the dermis. D Lymphatic malformation. The large lympatic channels in the papillary dermis a
re responsible for the clinical vesicular appearance of the skin (Courtesy of Dr
M. Wassef, Department of Pathology, Hôpital Lariboisière, Paris.)
105FT1.jpg|Table 105.1 Differences between vascular malformations
and infantile hemangiomas.
105FT2.jpg|Table 105.2 Current status of molecular genetics of va
scular anomalies. (CADASIL, cerebral autosomal dominant arteriopathy with su
bcortical infarcts and leukoencephalopathy; TGF-â, transforming growth fact
or-â; VEGFR-3, vascular endothelial growth factor receptor-3; VM, venous ma
lformation)
105FT3.jpg|Table 105.3 Investigative tools and when to use them.
106FF1.jpg|Fig. 106.1 Causes of leg ulcers.
106FF2.jpg|Fig. 106.2 Venous blood flow in the lower leg. Nor
mally, the calf muscle pumps venous blood towards the heart distally to proximal
ly against gravity, and from the superficial to deep venous systems. Venous ulce
rs are often secondary to venous reflux and/or calf muscle pump dysfunction. In
calf muscle pump dysfunction, the expected decrease in the venous pressure durin
g exercise does not occur and ‘venous hypertension’ occurs.
106FF3.jpg|Fig. 106.3 Theories of venous ulcer formation. The
theories include the presence of pericapillary cuffs due to leakage of fibrinog
en, binding of growth factors by leaked molecules, and the trapping of leukocyte
s with subsequent vascular damage.
106FF4.jpg|Fig. 106.4 Cholesterol emboli. Ischemia and necros
is with early ulcer formation.
106FF5.jpg|Fig. 106.5 Venous ulcer. The location in the gaite
r area is common. Note the surrounding hemosiderin pigmentation. (Courtesy of Dr
Ronald Rapini.)
106FF6.jpg|Fig. 106.6 Venous ulcer and stasis dermatitis. Not
e the erythema, crusting and scaling of the skin surrounding the ulcer of the me
dial malleolus.
106FF7.jpg|Fig. 106.7 Lipodermatosclerosis, chronic ulceration an
d lymphedema of the dependent portion of the pannus. The changes are similar
to those seen on the lower extremities.
106FF8.jpg|Fig. 106.8 Livedoid vasculitis. Multiple hemorrhag
ic crusts and small painful ulcers associated with hyperpigmentation.
106FF9.jpg|Fig. 106.9 A typical venous ulcer presents in the gait
er area. Note the irregular, slightly sloping border, relatively shallow dep
th, and abundant granulation tissue.
106FF10.jpg|Fig. 106.10 Bilateral lymphedema due to Milroy's dise
ase.
106FF11.jpg|Fig. 106.11 Elephantiasis nostras due to combined lym
phedema and venous insufficiency.
106FF12.jpg|Fig. 106.12 Arterial ulcer. The punched-out appea
rance and surrounding smooth shiny skin are common features. (Courtesy of Dr Ron
ald Rapini.)
106FF13.jpg|Fig. 106.13 Sites where pressure sensation is tested.
 These sites are the same as those at risk for the development of neuropathi
c ulcers.
106FF14.jpg|Fig. 106.14 Mal perforans ulcerations at pressure poi
nts on the plantar surface of the great toes. The patient had diabetic neuro
pathy.
106FF15.jpg|Fig. 106.15 Debridement of black eschar from a diabet
ic ulcer. Courtesy of Dr Ronald Rapini, M.D.
106FF16.jpg|Fig. 106.16 Management and prevention of neuropathic
foot ulcer in patients with diabetes mellitus. (Reproduced with permission f
rom Capulo et al. Current concepts: assessment and management of foot disease in
patients with diabetes. N Engl J Med. 1994;331:845–60.)
106FF17.jpg|Fig. 106.17 Sacral decubitus ulcer. Courtesy of D
r Ronald Rapini, M.D.
106FF18.jpg|Fig. 106.18 Black eschar of the heel at site of press
ure necrosis.
106FF19.jpg|Fig. 106.19 Most common sites for pressure ulcers.
106FF20.jpg|Fig. 106.20 National Pressure Ulcer Advisory Panel cl
assification of pressure ulcers. A Stage I: non-blanchable erythema of intac
t skin. This lesion is the heralding sign of impending skin ulceration. For dark
er-skinned individuals other signs may be indicators and include warmth, edema,
discoloration of the skin, and hardness. B Stage II: partial-thickness sk
in loss involving the epidermis, dermis, or both. This superficial lesion presen
ts as an abrasion, blister, or shallow crater. C Stage III: full-thicknes
s skin loss, in which subcutaneous tissue is damaged or necrotic and may extend
down into, but not including, the underlying fascia. This deep lesion presents a
s a crater and sometimes involves adjacent tissue. D Stage IV: full-thick
ness skin loss and extensive tissue necrosis, destruction to muscle, bone, or su
pporting structures such as tendon or joint capsule. Undermining or sinus tracts
can be present.
106FT1.jpg|Table 106.1 Comparison of clinical findings in the thr
ee major types of leg ulcer. Adapted with permission from Phillips TJ, Dover
JS. Leg ulcers. J Am Acad Dermatol. 1991;25:965–87.
106FT2.jpg|Table 106.2 Points to include in the history and physi
cal examination of patients with a leg ulcer. ASCVD, atherosclerotic cardiov
ascular disease; CTD, connective tissue disease. Adapted with permission from Ka
nj LF, Phillips TJ. Management of leg ulcers. Fitpatrick’s J Clin Dermatol
. 1994;Sept/Oct:52–60.
106FT3.jpg|Table 106.3 Causes of lymphedema.
106FT4.jpg|Table 106.4 Classes of compression stockings. Adap
ted with permission from Phillips TJ. Current approaches to venous ulcers and co
mpression. Dermatol Surg. 2001;27:611–21.
106FT5.jpg|Table 106.5 Types of compression therapy. Adapted
with permission from Choucair M, Phillips TJ. Compression therapy. Dermatol Surg
. 1998;24:141–8.
106FT6.jpg|Table 106.6 Classes of compression bandages.
106FT7.jpg|Table 106.7 Recommended dressings according to chronic
ulcer type. Adapted with permission from Bello YM, Phillips TJ. Therapeutic
dressings. Adv Dermatol. 2000;16;253–70.
106FT8.jpg|Table 106.8 Treatment of venous leg ulcers – cli
nical trials. *Comprilan over wool plus tricotix net. †Firs
t layer, wool; second layer, crepe; third layer, elastic conformable compression
bandage; fourth layer, coban. ‡Icthopaste with outer support (
Elastocrepe and Tubigrip).
106FT9.jpg|Table 106.9 Instructions for the patient with a diabet
ic or neuropathic ulcer.
107FF1.jpg|Fig. 107.1 Anatomical basis for the development of liv
edo.
107FF2.jpg|Fig. 107.2 Sneddon's syndrome. By staining with an
antibody that recognizes smooth muscle actin, subintimal proliferation of smoot
h muscle in an occluded vessel is demonstrated.
107FF3.jpg|Fig. 107.3 Livedo reticularis. A mottled or net-li

ke pattern is seen on the thigh.
107FF4.jpg|Fig. 107.4 Livedo reticularis associations.
107FF5.jpg|Fig. 107.5 Schemata of livedo reticularis (A) and live
do racemosa (B).
107FF6.jpg|Fig. 107.6 Antiphospholipid syndrome. Livedo racem
osa on the trunk of a patient with antiphospholipid syndrome.
107FF7.jpg|Fig. 107.7 Livedo racemosa associations.
107FF8.jpg|Fig. 107.8 Antiphospholipid syndrome. By MRI, whit
e lesions due to emboli are seen in subcortical areas.
107FF9.jpg|Fig. 107.9 Causes of retiform purpura. Purpura ful
minans due to sepsis (A), calciphylaxis (B) and cholesterol emboli
(C). These patients usually have areas of livedo reticularis or racemosa
as well, especially in the latter two entities. The intravascular clefts seen i
n the photomicrograph (C) are due to dissolution of cholesterol crystals during
fixation.
107FF10.jpg|Fig. 107.10 Unilateral nevoid telangiectasia. Not
e the segmental, unilateral distribution pattern of the telangiectasias. Courtes
y of Robert Hartman, M.D.
107FF11.jpg|Fig. 107.11 Angioma serpiginosum. A Grouped dark
red puncta on the arm in a serpiginous pattern. B Extensive copper-colore
d serpiginous telangiectasias on the trunk. B, courtesy of Ron Rapini, M.D.
107FF12.jpg|Fig. 107.12 Venous lake on the lip. The lesion is
soft and with compression, can be emptied of most of its blood content. Courtes
y of Ron Rapini, M.D.
107FF13.jpg|Fig. 107.13 Multiple spider angiomas in a patient wit
h liver disease. This patient was also jaundiced. Courtesy of Ron Rapini, M.
D.
107FF14.jpg|Fig. 107.14 Solitary angiokeratoma. Because of th
eir dark color, these lesions may resemble cutaneous melanoma. Courtesy of Jean
Bolognia, M.D.
107FF15.jpg|Fig. 107.15 Angiokeratoma circumscriptum. These g
rouped red-violet papules had been present since childhood. Courtesy of Jean Bol
ognia, M.D.
107FF16.jpg|Fig. 107.16 Evaluation of patients with flushing.
107FF17.jpg|Fig. 107.17 Nevus anemicus. The lesion is the are
a of pale blanching surrounded by erythema that occurred after application of an
ice cube. Courtesy of Ron Rapini, M.D.
107FT1.jpg|Table 107.1 Causes of telangiectasias.
107FT2.jpg|Table 107.2 Types of flushing reactions.
107FT3.jpg|Table 107.3 Flushing related to food additives.
107FT4.jpg|Table 107.4 Neurologic flushing.
107FT5.jpg|Table 107.5 Flushing due to drugs.
107FT6.jpg|Table 107.6 Flushing due to systemic diseases.
108FF1.jpg|Fig. 108.1 Cell cycle regulation. Cyclin waves, an
underlying mechanism for cell cycle progression, are illustrated inside the cel
l cycle. Proto-oncogenes acting as driving forces on the cell cycle (green traff
ic lights), are depicted in green. Tumor suppressor genes, regulating the G
1 checkpoint (red traffic light) of the cell cycle, are depicted in red. Y
ellow traffic light symbols represent checkpoints in the cell cycle.
108FF2.jpg|Fig. 108.2 Carcinogenesis: oncogenes vs tumor suppress
or genes. Oncogenes drive proliferation in a dominant fashion by gene amplif
ication or activating mutations in one allele. Tumor suppressor genes function a
s a brake on the cell cycle and act in a recessive fashion by loss-of-function (
inactivating mutations and/or deletions) in both alleles.
108FF3.jpg|Fig. 108.3 Apoptosis. Various triggering events ar
e depicted above the factors involved in the apoptotic pathways. Consequences of
induced apoptosis are shown at the bottom of the figure.
108FF4.jpg|Fig. 108.4 The functional p53 gene. These domains
involved in transactivation, sequence-specific DNA binding, oligomerization and
auto-inhibition. Binding sites for Mdm2 and TBP proteins are noted. TBP, TATA bo
x-binding protein.
108FF5.jpg|Fig. 108.5 Three dimensional view of the p53 protein. Three units of the normally tetramerized active p53 are shown surrounding th
e DNA double helix. The β-sheets are shown in yellow and α-helices are
depicted in red. From Sayle RA, Milner-White EJ. RASMOL: biomolecular graphics
for all. Trends Biochem Sci. 1995;20:374; Cho Y, et al. Crystal structure of a p
53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science. 1
994;265:346–55.
108FF6.jpg|Fig. 108.6 Sites of mutations in p53 gene.
The frequency of mutations are shown with respect to specific codons within the
p53 gene in all cancers (top panel) and skin cancer (basal cell carcinoma
+ squamous cell carcinoma; bottom panel). Numbers represent hotspots for p53
 mutations. From Hernandez-Boussard T, et al. IARC p53 mutation datab
ase. Human Mutat. 1999;14:1–8.
108FF7.jpg|Fig. 108.7 p53 immunoreactivity. The photomicrogra
phs of two different patterns of p53 immunoreactivity found in normal ski
n. A Dispersed pattern of p53 positivity representing a normal reactive r
esponse to DNA damage (e.g. single exposure to UVB). B Epidermal p53 clone representing a clonal expansion of morphologically normal keratinocytes
with a p53 mutation. The latter is seen in chronically sun-exposed skin.
108FF8.jpg|Fig. 108.8 Central features of Hedgehog–Patched
signaling. Unbound Patched silences Smoothened signaling (A). As Hedg
ehog binds to its receptor (Patched), the repression of Smoothened is removed an
d signals are transduced via Gli to the nucleus (B). C Inactivatin
g mutations in PTCH simulate Hedgehog binding and result in constitutive
activation of GLI and downstream target genes.
108FF9.jpg|Fig. 108.9 Subclones within a basal cell carcinoma. A common p53 mutation (red cross) is found in different parts of the tu
mor. Despite indistinguishable morphology, different parts of individual BCCs ha
ve acquired additional mutations in the p53 gene (blue, yellow and green
crosses). Boxes illustrate the two p53 alleles. Note normal p53 st
atus (outlined in yellow) in overlying epidermal keratinocytes.
108FF10.jpg|Fig. 108.10 The multi-step development of squamous ce
ll carcinoma. UV irradiation of normal skin induces mutations in keratinocyt
es and facilitates clonal expansion of keratinocytes with a mutated p53 g
ene. Additional mutations (including a second p53 mutation) that affect g
enes controlling proliferation, cell migration and cell death provide for select
ive growth advantage and cause genomic instability. The final result is metastat
ic tumor cells, capable of growing in regional lymph nodes and internal organs.
108FT1.jpg|Table 108.1 Examples of oncogenes and tumor suppressor
genes implicated in carcinogenesis. *Phosphorylates tyrosine residues. &#82
24;Phosphorylates serine and threonine residues.
108FT2.jpg|Table 108.2 Examples of mechanisms and molecules invol
ved in carcinogenesis. EGF, epidermal growth factor; TGF, transforming growt
h factor; IGF, insulin-like growth factor.
108FT3.jpg|Table 108.3 Examples of genes where transcription is i
nfluenced by the p53 tetramer.
109FF1.jpg|Fig. 109.1 Xeroderma pigmentosum. Multiple skin ca
ncers on the face of a 12-year-old Hispanic boy.
109FF2.jpg|Fig. 109.2 Actinic keratoses. AKs on the hand. Cou
rtesy of Ron Rapini, MD.
109FF3.jpg|Fig. 109.3 Actinic cheilitis. The lower lip has mo
ttled pigmentation and is scaly. Two angiomas are present. Note that the upper l
ip is spared because of less exposure to solar radiation, a common finding. Cour
tesy of Ron Rapini, MD.
109FF4.jpg|Fig. 109.4 Squamous cell carcinoma in situ, Bow
en's type. Fiery red, scaling plaque on the chest.
109FF5.jpg|Fig. 109.5 Squamous cell carcinoma in situ, ery
throplasia of Queyrat type. Extensive, velvety erythematous plaque covering
the distal dorsal penis shaft.

109FF6.jpg|Fig. 109.6 Squamous cell carcinoma. Large, exophyt
ic, centrally keratotic red plaque on the midline vermillion lower lip.
109FF7.jpg|Fig. 109.7 Squamous cell carcinomas. Two separate
tumors with different morphologies, on the left preauricular cheek.
109FF8.jpg|Fig. 109.8 Verrucous carcinoma. Extensive tumor on
the plantar aspect of the right foot, of over ten years duration. Amputation wa
s required.
109FF9.jpg|Fig. 109.9 Histology of the acantholytic variant of ac
tinic keratosis. Prominent cytologic atypia of the basilar keratinocytes is
seen. There is loss of intercellular cohesion resulting in ‘floating&#8217
; keratinocytes within a clefted epithelium.
109FF10.jpg|Fig. 109.10 Histology of the bowenoid variant of acti
nic keratosis. Cytologic atypia of keratinocytes is present involving the fu
ll thickness of the epidermis, but lacking follicular and adnexal epithelial inv
olvement. There is overlying alternating orthohyperkeratosis and parakeratosis o
f the stratum corneum.
109FF11.jpg|Fig. 109.11 Histology of squamous cell carcinoma i
n situ. Keratinocytic atypia of the entire epidermal thickness is seen w
ith significant pleomorphism and crowding of cells, as well as scattered mitotic
figures at suprabasal levels.
109FF12.jpg|Fig. 109.12 Histology of squamous cell carcinoma.
This biopsy from a pseudoglandular squamous cell carcinoma shows acantholysis w
ithin the invasive islands. Courtesy of Ron Rapini, MD.
109FF13.jpg|Fig. 109.13 Histology of poorly-differentiated squamo
us cell carcinoma. There are large islands of markedly atypical cells with a
bundant cytoplasm. Numerous mitotic figures are seen, including bizarre forms. O
ccasional foci of keratinization are identified.
109FF14.jpg|Fig. 109.14 Histology of undifferentiated squamous ce
ll carcinoma. A large island of anaplastic cells with clear cytoplasmic feat
ures infiltrates the dermis. Scattered mitotic figures are seen. Obvious keratin
ization is not identified, however immunohistochemical stains for cytokeratins c
onfirmed the keratinocytic nature of this neoplasm.
109FF15.jpg|Fig. 109.15 Histology of acantholytic squamous cell c
arcinoma. Left panel: Variably sized nests and islands of atypical, dyscohes
ive keratinocytes are seen, forming pseudoglandular structures in the dermis. Ri
ght panel: Prominent acantholysis and dyskeratosis are identified.
109FF16.jpg|Fig. 109.16 Biopsy of keratoacanthoma. Note the k
eratin-filled crater. Courtesy of Ron Rapini, MD.
109FF17.jpg|Fig. 109.17 Nodular BCC. Pearly plaque with promi
nent overlying telangectasias, on the left infraorbital cheek.
109FF18.jpg|Fig. 109.18 Pigmented nodular BCC. Arising in a d
arkly pigmented individual in the right nasolabial fold.
109FF19.jpg|Fig. 109.19 Superficial spreading BCC. Erythemato
us plaques of superficial BCC can resemble eczematous or papulosquamous diseases
, and can be difficult to distinguish from Bowen's disease and lichenoid keratos
is. Courtesy of Ron Rapini, MD.
109FF20.jpg|Fig. 109.20 Infiltrative BCC. Extensive, indurate
d lesion in the mid-right infraorbital cheek, creating significant ectropion of
the lower eyelid.
109FF21.jpg|Fig. 109.21 Histology of basal cell carcinoma. No
te the peripheral palisading of nuclei and stromal reaction. Courtesy of Ron Rap
ini, MD.
109FF22.jpg|Fig. 109.22 Histology of superficial basal cell carci
noma. Discrete nests of small basaloid cells are present with attachment to
the overlying epidermis. Prominent peritumoral clefting is seen.
109FF23.jpg|Fig. 109.23 Fibroepithelioma of Pinkus. This vari
ant of basal cell carcinoma has delicate reticulated basaloid strands in a pale
stroma. Courtesy of Ron Rapini, MD.
109FF24.jpg|Fig. 109.24 NCCN practice guidelines, version 2001, f
or BCC. *Any high-risk factor places the patient in a high-risk category.

109FF25.jpg|Fig. 109.25 NCCN practice guidelines, version 2001, f
or SCC.
109FF26.jpg|Fig. 109.26 High-risk mask area of the face. NMSC
s that develop in these regions are more likely to recur and metastasize than th
ose that develop on the trunk and extremities.
109FT1.jpg|Table 109.1 Influence of skin color on epidemiology of
NMSC.
109FT2.jpg|Table 109.2 Incidence rates per year (per 100 000) of
BCC and SCC by geographic location5.
109FT3.jpg|Table 109.3 Annual NMSC mortality rates in subjects wi
th lightly pigmented skin4.
109FT4.jpg|Table 109.4 Risk factors for development of BCCs and S
CCs.
109FT5.jpg|Table 109.5 UV exposure and NMSC development.
109FT6.jpg|Table 109.6 Immunostaining patterns in three pagetoid
diseases
109FT7.jpg|Table 109.7 Influence of tumor thickness on SCC metast
atic rate72.
109FT8.jpg|Table 109.8 Histologic simulants of BCC.
109FT9.jpg|Table 109.9 Risk factors for recurrence of NMSC (modif
ied from ref. 68)
110FF1.jpg|Fig. 110.1 Seborrheic keratoses. Sharply demarcate
d, pigmented papule and plaques with a papillomatous surface and horn pseudocyst
s. Note the ‘stuck-on’ appearance.
110FF2.jpg|Fig. 110.2 Seborrheic keratosis, acanthotic type.
The thickened epidermis consists of basaloid cells. A horn pseudocyst is present
.
110FF3.jpg|Fig. 110.3 Seborrheic keratosis, reticulated type.
The basaloid cells are organized in a reticulated architecture.
110FF4.jpg|Fig. 110.4 Seborrheic keratosis, irritated type. T
he cells are less basaloid than in other types of seborrheic keratosis, and ther
e are prominent squamous eddies.
110FF5.jpg|Fig. 110.5 Differential diagnosis of epithelial prolif
eration.
110FF6.jpg|Fig. 110.6 Dermatosis papulosis nigra. Multiple hy
perpigmented papules with typical location on the cheeks.
110FF7.jpg|Fig. 110.7 Inverted follicular keratosis. An endop
hytic proliferation of keratinocytes with prominent squamous eddies is seen.
110FF8.jpg|Fig. 110.8 Clear cell acanthoma. A An erythematous
papule on the distal lower extremity; note the peripheral scale and erosion in
the superior position. B A psoriasiform epidermis contains large pale ker
atinocytes. Courtesy of Ron Rapini, M.D.
110FF9.jpg|Fig. 110.9 Warty dyskeratoma. A portion of a cup-s
haped lesion is shown. The central keratotic plug is seen on the left. The lower
portion of the cup is occupied by numerous villi with acantholytic epithelium.
110FF10.jpg|Fig. 110.10 Evaluation of the histologic findings of
suprabasilar acantholysis.
110FF11.jpg|Fig. 110.11 Porokeratosis. A Porokeratosis of Mib
elli on the hand of a child. B Actinic porokeratosis in a renal transplan
t patient with significant solar damage. Note the narrow, elevated rim. C
Multiple lesions of punctate porokeratosis on the palm.
110FF12.jpg|Fig. 110.12 Porokeratosis. The coronoid lamella,
a narrow column of parakeratotic cells, is the typical histologic feature of por
okeratosis. Note the absence of the granular layer beneath the coronoid lamella.
110FF13.jpg|Fig. 110.13 Inflammatory linear verrucous epidermal n
evus (ILVEN). Linear erythematous scaly plaque with a psoriasiform appearanc
e on the leg.
110FF14.jpg|Fig. 110.14 Inflammatory linear verrucous epidermal n
evus (ILVEN). The epidermis is acanthotic, and zones of parakeratosis devoid
of a granular layer alternate with zones of orthohyperkeratosis.

110FF15.jpg|Fig. 110.15 Epidermolytic hyperkeratosis. There i
s clearing of the cytoplasm of keratinocytes, coarsening of keratohyaline granul
es and overlying hyperkeratosis.
110FF16.jpg|Fig. 110.16 Flegel's disease (hyperkeratosis lenticul
aris perstans). A Multiple symmetric keratotic papules are seen on the shins
. B The spinous layer is markedly thinned, and there is a lichenoid infil
trate and obvious hyperkeratosis.
110FF17.jpg|Fig. 110.17 Cutaneous horn. This cutaneous horn a
rose from an actinic keratosis.
110FF18.jpg|Fig. 110.18 Benign lichenoid keratosis. A A pink
papule. B A lichenoid infiltrate obscures the dermo–epidermal junct
ion. The keratinocytes at the junction show vacuolar alteration. A necrotic kera
tinocyte (Civatte body) is seen in the upper epidermis.
110FF19.jpg|Fig. 110.19 Confluent and reticulated papillomatosis.
 Multiple hyperpigmented verrucous papules form a reticulated pattern at the
periphery (right) and are largely confluent at the center of the affected area
(left).
111FF1.jpg|Fig. 111.1 Approach to a cyst with stratified squamous
epithelium. *Diameter >2 mm.
111FF2.jpg|Fig. 111.2 Epidermoid cyst. Typical clinical appea
rance of an epidermoid cyst. Pores are present in this example.
111FF3.jpg|Fig. 111.3 Primary cysts of follicular origin. Ana
tomic origin of cysts derived from the pilosebaceous unit. (Adapted from Requena
and Yus .)
111FF4.jpg|Fig. 111.4 Inflamed epidermoid cyst. Such painful
inflammatory reactions to cyst rupture are a frequent cause for presentation to
a physician.
111FF5.jpg|Fig. 111.5 Histology of an epidermoid cyst. The cy
st wall shows epidermal keratinization including a granular layer. Laminated ker
atin cyst contents are seen.
111FF6.jpg|Fig. 111.6 Trichilemmal cyst. Trichilemmal cysts a
re most commonly seen on the scalp.
111FF7.jpg|Fig. 111.7 Histology of a trichilemmal cyst. The c
yst wall shows swollen keratinocytes with abrupt keratinization without formatio
n of a granular layer. Homogenous keratin fills the cyst.
111FF8.jpg|Fig. 111.8 Proliferating trichilemmal cyst. An enl
arging cystic nodule on the scalp of an elderly female.
111FF9.jpg|Fig. 111.9 Histology of a proliferating trichilemmal c
yst. Irregular bands and nodules of squamous epithelium show central areas o
f abrupt keratinization.
111FF10.jpg|Fig. 111.10 Eruptive vellus hair cysts. Pigmented
small papules seen on the thigh of a young woman.
111FF11.jpg|Fig. 111.11 Histology of a vellus hair cyst. A sm
all cyst shows epidermoid keratinization of the cyst wall and numerous vellus ha
irs in the lumen.
111FF12.jpg|Fig. 111.12 Steatocystoma multiplex. Numerous cys
tic nodules are seen on the trunk.
111FF13.jpg|Fig. 111.13 Histology of steatocystoma. A flatten
ed sebaceous lobule is seen in the cyst wall, which is lined by a thin eosinophi
lic cuticle.
111FF14.jpg|Fig. 111.14 Apocrine hidrocystoma. A single bluis
h translucent papule is seen on the lower lid.
111FF15.jpg|Fig. 111.15 Eccrine hidrocystoma. Numerous transl
ucent papules are seen on the lower lid.
111FF16.jpg|Fig. 111.16 Histology of apocrine hidrocystoma. T
he cyst wall shows typical apocrine decapitation secretion.
111FF17.jpg|Fig. 111.17 Histology of eccrine hidrocystoma. Tw
o layers of flattened epithelium form the cell wall.
111FF18.jpg|Fig. 111.18 Histology of thyroglossal duct cyst.
Thyroid follicles are seen adjacent to a cyst lined by ciliated epithelium.

111FF19.jpg|Fig. 111.19 Omphalomesenteric duct cyst. This pin
k papule in the umbilicus of this infant showed gastrointestinal epithelium hist
ologically.
111FF20.jpg|Fig. 111.20 Mucocele. A bluish translucent papule
on the lower mucosal lip.
111FF21.jpg|Fig. 111.21 Digital mucous cyst. A translucent pa
pule on the dorsal distal phalanx of the finger causing a depression in the nail
plate.
111FF22.jpg|Fig. 111.22 Pseudocyst of the auricle. Erythemato
us firm nodule on the ear.
111FT1.jpg|Table 111.1 The three main categories of cutaneous cys
t.
112FF1.jpg|Fig. 112.1 Trichofolliculoma. Wispy vellus hairs e
merge from a skin-colored papule with a dilated central pore. Courtesy of Yale R
112FF2.jpg|Fig. 112.2 Trichofolliculoma, viewed at scanning magni
fication. There is a central patulous follicular infundibulum, from which fu
lly formed or nearly fully formed follicles radiate.
112FF3.jpg|Fig. 112.3 Fibrofolliculoma. Several skin-colored
papules are present on the ear.
112FF4.jpg|Fig. 112.4 Nevus sebaceus. Yellowish verrucous pla
que on the scalp. Courtesy of Ron Rapini, M.D.
112FF5.jpg|Fig. 112.5 Nevus sebaceus. Yellow-brown verrucous
plaque in which a bluish ‘basal cell carcinoma’ developed. Courtesy
of Ron Rapini, M.D.
112FF6.jpg|Fig. 112.6 Nevus sebaceus. Medium magnification re
veals expansion of the epidermis in papillated fashion, much like the pattern of
an epidermal nevus, jointly with adnexal malformation, with enlarged sebaceous
lobules and clusters of follicular germinative cells positioned along the epider
mal-dermal junction.
112FF7.jpg|Fig. 112.7 Chondroid syringoma. Nodule of chin. Co
urtesy of Ron Rapini, M.D.
112FF8.jpg|Fig. 112.8 Mixed tumor (chondroid syringoma) with over
t apocrine differentiation. At medium magnification, there is a hamartomatou
s pattern, with large branching tubules arrayed within a mucinous stroma that co
ntains lipocytes. Conspicuous apocrine differentiation with a ‘decapitatio
n’ pattern is evident in the inset.
112FF9.jpg|Fig. 112.9 Mixed tumor (chondroid syringoma) with duct
al differentiation. This pattern, commonly referred to as the ‘eccrine
’ type of mixed tumor, shows small syringoma-like ducts positioned in ampl
e stroma reminiscent of hyaline cartilage.
112FF10.jpg|Fig. 112.10 Trichoepithelioma. Numerous skin-colo
red papules on the mid-face.
112FF11.jpg|Fig. 112.11 Trichoepithelioma (trichoblastoma). T
his ‘classical’ trichoepithelioma is composed mostly of clusters of
follicular germinative cells but also shows superficial follicular differentiati
on, with small keratinizing cystic spaces. Note that clefts within the prolifera
tion are between stromal elements, in contrast to the clefts between tumor and s
troma that are characteristic of basal cell carcinoma.
112FF12.jpg|Fig. 112.12 Desmoplastic trichoepithelioma. It is
composed of thin strands of basaloid (follicular germinative) cells, arrayed in
sclerotic stroma. Much like conventional trichoepithelioma, there are foci of s
uperficial follicular keratinization.
112FF13.jpg|Fig. 112.13 Pilomatricoma. A nodule on the cheek.
Courtesy of Yale Residents Slide Collection.
112FF14.jpg|Fig. 112.14 Pilomatricoma. At high magnification,
this longstanding example is notable for anucleate keratinized matrical cells (
‘shadow’ cells) and a surrounding granulomatous reaction.
112FF15.jpg|Fig. 112.15 Trichilemmoma. This benign neoplasm w
ith follicular differentiation shows a verrucous surface with hypergranulosis. T

his pattern, which is commonly present, has suggested to some that these lesions
may be induced by papillomavirus. The inset shows follicular outer sheath diffe
rentiation, with pale keratinocytes surrounded by a palisade of small basal cell
s, adjacent to which is a densely eosinophilic thickened basement membrane.
112FF16.jpg|Fig. 112.16 Isthmicoma (tumor of follicular infundibu
lum). The microscopic pattern of TFI is subtle, and thus the lesion is somet
imes overlooked or interpreted as a reticulate seborrheic keratosis. There are s
trands of pale pinkish keratinocytes with isthmic differentiation arrayed in ret
iculate fashion within the papillary dermis. The strands display multifocal atta
chment to the epidermal surface and also commonly interconnect with existent fol
licular structures.
112FF17.jpg|Fig. 112.17 Trichoadenoma. This lesion consists a
lmost exclusively of small keratinizing cystic spaces that display follicular is
thmic and infundibular keratinization. There are also a few strands of basaloid
cells and sclerotic stroma, similar to the pattern observed in desmoplastic tric
hoepithelioma.
112FF18.jpg|Fig. 112.18 Proliferating follicular-cystic neoplasm.
 This complex multicystic neoplasm shows abrupt keratinization, similar to t
he pattern exhibited at the follicular isthmus. Although it can be difficult to
determine whether these lesions are benign or malignant, this example was well c
ircumscribed and was eradicated by simple enucleation.
112FF19.jpg|Fig. 112.19 Sebaceous hyperplasia. Skin-colored t
o yellowish papules with a central dell are evident. Courtesy of Yale Residents
Slide Collection.
112FF20.jpg|Fig. 112.20 Sebaceous adenoma (sebaceoma). This h
igh magnification view shows a background of basaloid seboblastic cells punctuat
ed by scattered mature sebocytes with coarsely vacuolated cytoplasm. The neoplas
m was large but sharply circumscribed at low magnification.
112FF21.jpg|Fig. 112.21 Sebaceous carcinoma. At high magnific
ation, there are cells with atypical nuclei and ample coarsely vacuolated cytopl
asm. There are also many necrotic cells with pyknotic nuclei.
112FF22.jpg|Fig. 112.22 Syringoma. Aggregated skin-colored pa
pules are present. Courtesy of Yale Residents Slide Collection.
112FF23.jpg|Fig. 112.23 Syringoma. This superficial adnexal n
eoplasm consists of nests of cells with pale cytoplasm positioned within sclerot
ic stroma. Many nests show central ductal differentiation with a compact eosinop
hilic cuticle.
112FF24.jpg|Fig. 112.24 Poroma. A biopsy specimen is necessar
y to establish a definitive diagnosis. Courtesy of Yale Residents Slide Collecti
on.
112FF25.jpg|Fig. 112.25 Poroma, juxta-epidermal pattern. This
poroma displays a pattern common to both eccrine and apocrine poroma. There are
interanastomosing cords composed of small compact ‘poroid’ cells, a
nd the intervening stroma is highly vascularized and resembles granulation tissu
e.
112FF26.jpg|Fig. 112.26 Poroma, intradermal pattern. At low m
agnification, this lesion was a well circumscribed dermal nodule. This high magn
ification shows conspicuous foci of ductal differentiation and also a focus of n
ecrosis en masse, a finding common to poroma that is uncommon in other benign ne
oplasms.
112FF27.jpg|Fig. 112.27 Hidradenoma. This focus was obtained
from a large well circumscribed nodule. At high magnification, the process is co
mposed of cells with small uniform nuclei and ample cytoplasm that often is pale
or shows overt clear cell change. There is a cystic focus present; lesions that
display prominent cystic change have been referred to as ‘solid-cystic&#8
217; hidradenoma.
112FF28.jpg|Fig. 112.28 Syringocystadenoma papilliferum. Grou
ped keratotic papules and nodules
112FF29.jpg|Fig. 112.29 Syringocystadenoma papilliferum. This
condition consists of papillary foci lined by columnar cells that usually displ
ay overt apocrine differentiation. The cores of papillae are usually stuffed wit
h lymphocytes and many plasma cells.
112FF30.jpg|Fig. 112.30 Hidradenoma papilliferum. This well c
ircumscribed dermal nodule is composed of fronds and papillae with a connective
tissue core lined by a bilayer of cells, with columnar apocrine cells positioned
above a cuboidal monolayer of myoepithelial cells.
112FF31.jpg|Fig. 112.31 Spiradenoma. The tumor shows a multin
odular pattern with a small number of relatively large nodules assembled in a gi
ven lesion. This subcutaneous nodule shows the typical trabecular pattern exhibi
ted by each nodule, with darkly staining cells lining trabeculae and pale cells
with pink cytoplasm in their centers. There are usually many superimposed lympho
cytes.
112FF32.jpg|Fig. 112.32 Cylindroma. While numerous tumors agg
regated on the scalp are called turban tumors, solitary lesions are clinically n
onspecific. Courtesy of Yale Residents Slide Collection.
112FF33.jpg|Fig. 112.33 Cylindroma. A close relative of spira
denoma and sometimes coexistent with it, cylindroma is distinctive for its puzzl
e-like pattern, with small nests of basaloid cells that are assembled in a compl
ex mosaic pattern. Many nests are circumferentially enveloped by a dense eosinop
hilic band of basement membrane material.
112FF34.jpg|Fig. 112.34 Porocarcinoma. Rapid growth and erosi
on or ulceration accompany this malignant adnexal tumor. Courtesy of Yale Reside
112FF35.jpg|Fig. 112.35 Microcystic adnexal carcinoma. This t
umor presents as a slowly expanding, firm plaque. Courtesy of Yale Residents Sli
de Collection.
112FF36.jpg|Fig. 112.36 Microcystic adnexal carcinoma. This d
eeply infiltrative carcinoma shows a biphasic microscopic pattern, with both duc
tular differentiation and superficial follicular keratinization. The high magnif
ication inset shows conspicuous ductal differentiation and is also notable for a
lack of cytological atypism, which sometimes leads to misdiagnosis as a benign
lesion.
112FF37.jpg|Fig. 112.37 Porocarcinoma. There are irregularlyshaped nests of neoplastic cells that infiltrate deeply, with this image obtaine
d at the level of the superficial subcutis. The largest nest shows central foci
of ductular differentiation.
112FF38.jpg|Fig. 112.38 Porokeratotic eccrine ostial and dermal duct
nevus. Markedly hyperkeratotic spines arise from dilated eccrine ostia, corresp
onding to the histologic findings of coronoid lamellae. Courtesy of Yale Residen
ts Slide Collection.
112FF39.jpg|Fig. 112.39 Papillary adenocarcinoma of the digit. This entity, originally recognized as ‘aggressive digital papillary aden
oma,’ was ‘aggressive’ because it was a form of carcinoma. Thi
s image shows solid and tubular and papillary foci, with small foci of necrosis
in some tubules. Mitotic figures are easily identifiable in these lesions.
113FF1.jpg|Fig. 113.1 Ephelides. Small, well-circumscribed ta
n macules on fair skin. Courtesy of Ron Rapini, M.D.
113FF2.jpg|Fig. 113.2 Café-au-lait macule. Well-circumsc
ribed, homogeneous, light brown patch.
113FF3.jpg|Fig. 113.3 Becker's melanosis. Large, unilateral,
hyperpigmented, hypertrichotic, and slightly elevated plaque on left shoulder.
113FF4.jpg|Fig. 113.4 Solar lentigine. Sharply demarcated, un
iform, tan macules on sun-exposed skin.
113FF5.jpg|Fig. 113.5 Solar lentigine. Hyperpigmented elongat
ed rete ridges with diffuse increase in non-nested melanocytes, and solar elasto
sis. Courtesy of Ron Rapini, M.D.
113FF6.jpg|Fig. 113.6 Lentigo simplex (labial lentigo). Sharp
ly demarcated, tan macule on the lower lip.
113FF7.jpg|Fig. 113.7 Labial lentigo. Hyperpigmented rete rid
ges are broader than in the average lentigo.

113FF8.jpg|Fig. 113.8 Mongolian spots. Ill-defined gray to st
eel-blue patches in the lumbosacral area.
113FF9.jpg|Fig. 113.9 Nevus of Ota. Ill-defined, unilateral,
mottled blue to brown patch involving the skin, sclera and mucous membranes of t
he first and second branches of the trigeminal nerve.
113FF10.jpg|Fig. 113.10 Nevus of Ota. Sparse dermal spindled
melanocytes and melanophages. Courtesy of Ron Rapini, M.D.
113FF11.jpg|Fig. 113.11 Common blue nevus. Well-circumscribed
, small, blue dome-shaped papule on dorsum of the wrist. Courtesy of Ron Rapini,
M.D.
113FF12.jpg|Fig. 113.12 Cellular blue nevus. Well-circumscrib
ed, moderately large blue dome-shaped papule.
113FF13.jpg|Fig. 113.13 Common blue nevus. Heavily pigmented
dermal spindled melanocytes and melanophages, denser than in Mongolian spot or n
evus of Ota.
113FF14.jpg|Fig. 113.14 Cellular blue nevus. Denser, more plu
mp spindled melanocytes than in common blue nevus.
113FF15.jpg|Fig. 113.15 Deep penetrating nevus. Fascicles of
pigmented melanocytes push into the adipose layer. Courtesy of Ron Rapini, M.D.
113FF16.jpg|Fig. 113.16 Junctional nevus. Brown macule.
113FF17.jpg|Fig. 113.17 Compound nevus. Uniformly brown, slig
htly elevated papule. Courtesy of Ron Rapini, M.D.
113FF18.jpg|Fig. 113.18 Dermal nevus. Light tan, raised papul
e with hair.
113FF19.jpg|Fig. 113.19 Compound nevus. Nests of melanocytes
in the dermis and at the dermal-epidermal junction.
113FF20.jpg|Fig. 113.20 Halo nevus. Depigmented macular halo
surrounding a central dark brown papule.
113FF21.jpg|Fig. 113.21 Melanocytic nevus of acral skin. Smal
l brown macule on the palm of the hand. Courtesy of Ron Rapini, M.D.
113FF22.jpg|Fig. 113.22 Compound acral nevus. Note the occasi
onal pagetoid melanocytes. Courtesy of Ron Rapini, M.D.
113FF23.jpg|Fig. 113.23 Nevus spilus. Tan patch with foci of
tan and brown macules and papules.
113FF24.jpg|Fig. 113.24 Recurrent melanocytic nevus. Note the
depressed scar at the site of the shave, with repigmentation. Courtesy of Ron R
apini, M.D.
113FF25.jpg|Fig. 113.25 Spitz nevus. Red papule on the ear of
a child. Courtesy of Ron Rapini, M.D.
113FF26.jpg|Fig. 113.26 Spitz nevus. Small, well-circumscribe
d, dome-shaped dark brown papule in a 10-year old child.
113FF27.jpg|Fig. 113.27 Agminated Spitz nevi.
113FF28.jpg|Fig. 113.28 Spitz nevus. Sharply demarcated proli
feration of spindled and epithelioid melanocytes, with clefts around nests and e
pithelial hyperplasia. Courtesy of Ron Rapini, M.D.
113FF29.jpg|Fig. 113.29 Spitz nevus. ‘Raining-down&#821
7; effect of melanocytes from hyperplastic epidermis. Courtesy of Ron Rapini, M.
D.
113FF30.jpg|Fig. 113.30 Spitz nevus. Atypical epithelioid mel
anocytes. Courtesy of Ron Rapini, M.D.
113FF31.jpg|Fig. 113.31 Pigmented spindle cell nevus. Pigment
ed spindled cells within a small papule. Courtesy of Ron Rapini, M.D.
113FF32.jpg|Fig. 113.32 Atypical melanocytic nevi. Multiple p
igmented macules and papules on the back.
113FF33.jpg|Fig. 113.33 Erythematous variant of atypical melanocy
tic nevus. Irregular bordered, erythematous, brown and tan papule.
113FF34.jpg|Fig. 113.34 Targetoid variant of atypical melanocytic
nevus. Tan macule with dark brown rim.
113FF35.jpg|Fig. 113.35 Atypical melanocytic nevus. Elongated
rete ridges, bridging between rete ridges, fibroplasia, and sparse lymphocytes
are features. Cytologic atypia is usually mild. Courtesy of Ron Rapini, M.D.
113FF36.jpg|Fig. 113.36 Atypical melanocytic nevus. Follow-up
schedule and photography for clinically atypical melanocytic nevi. *Advocated b
y some authors.
113FF37.jpg|Fig. 113.37 Small congenital melanocytic nevus.
113FF38.jpg|Fig. 113.38 Giant congenital melanocytic nevus.
113FF39.jpg|Fig. 113.39 Congenital melanocytic nevus. Scannin
g view with nests extending down adnexal structures. Courtesy of Ron Rapini, M.D
.
113FF40.jpg|Fig. 113.40 Congenital melanocytic nevus. Melanoc
ytes often extend in a single-file pattern and invade an arrector pili muscle he
re. Courtesy of Ron Rapini, M.D.
113FF41.jpg|Fig. 113.41 Congenital melanocytic nevus. Melanoc
ytes extending along sweat ducts. Courtesy of Ron Rapini, M.D.
113FT1.jpg|Table 113.1 Comparative clinical features of ephelides
and solar lentigines.
113FT2.jpg|Table 113.2 Diseases and syndromes associated with caf
é-au-lait macules.
113FT3.jpg|Table 113.3 Special forms of lentigo simplex and assoc
iated syndromes.
113FT4.jpg|Table 113.4 Assessment of atypical Spitz tumors in chi
ldren and adolescents for risk for metastasis. Total score and risk for meta
stasis: 0–2, low risk; 3–4, intermediate risk; 5–11, high risk
.
113FT5.jpg|Table 113.5 Comparison of Spitz tumor and melanoma.
113FT6.jpg|Table 113.6 Nevus phenotypes.
113FT7.jpg|Table 113.7 Melanoma risk associated with clinical AMN
. Comparison of occurrence in melanoma patients versus controls. *Relatively
risk for one or two atypical nevi, 2.1; for three or more atypical nevi, 4.5. &
#8224;Relatively risk for one to five atypical nevi, 3.8; for six or more atypic
al nevi, 6.3.
113FT8.jpg|Table 113.8 Clinical characteristics of common acquire
d nevi, atypical melanocytic nevi and malignant melanoma.
114FF1.jpg|Fig. 114.1 Molecular pathogenesis of melanoma developm
ent. CDKN2A (INK4a/ARF) encodes two separate gene products p16 and p1
4ARF, which are both negative regulators of cell cycle progression. The p16 prot
ein executes its effects by competitive inhibition of cyclin-dependent kinase 4
(CDK4). CDK4 interacts with cyclin D and phosphorylates the master gatekeeper re
tinoblastoma protein (Rb). Phosphorylation of Rb will lead to S phase progressio
n and ultimately cellular division and proliferation. An intact p16 protein is e
ssential for cell cycle arrest. The net effect of CDKN2A mutation with lo
ss of p16 function will increase the likelihood that mutagenic DNA escapes repai
r before cell division. The second gene product p14ARF binds to MDM2 and regulat
es melanocyte growth through effects on the p53 ‘guardian of the genome&#8
217; pathway. MDM2 accelerates the destruction of p53. The net effect of CDKN2A
mutation with loss of p14ARF function is p53 loss with enhanced growth/survival
of altered cells.
114FF2.jpg|Fig. 114.2 Anti-melanoma immune response involves migr
ation of dendritic cells into secondary lymphoid organs. Activation of melan
oma-specific CD8 T cells is dependent on the migration of tumor antigen loaded p
rofessional antigen presenting cells (dendritic cells) from the tumor site to a
draining lymph node. Here, melanoma antigens are presented to CD8 T cells in the
presence of co-stimulatory molecules as well as CD4 helper T cells which is the
decisive step of CD8 T cell activation. Activated T cells upregulate chemokine
receptors and adhesion molecules that enables them to enter tissue sites were me
tastasis are located.
114FF3.jpg|Fig. 114.3 Age-adjusted incidence of melanoma in the U
S from 1969–1998. The incidence has increased for both the male and fe
male population, while an early indication of a plateau or regression may be obs

erved in recent years. This might be related to the effects of public health cam
paigns. Data from the Surveillance, Epidemiology, and End Results (SEER) program
of the National Cancer Institute, 2001.
114FF4.jpg|Fig. 114.4 Age-adjusted mortality of melanoma in the U
S from 1969–1998. Mortality has increased especially for male populati
on in contrast to the female population. Data from the Surveillance, Epidemiolog
y, and End Results (SEER) program of the National Cancer Institute, 2001.
114FF5.jpg|Fig. 114.5 Melanoma in situ. Note the macul
ar character, indistinct defined borders and variations in color.
114FF6.jpg|Fig. 114.6 Melanoma in situ. Tan to dark-br
own macule with irregular outline.
114FF7.jpg|Fig. 114.7 Melanoma. This small lesion is only 5&n
bsp;mm at its greatest diameter.
114FF8.jpg|Fig. 114.8 Melanoma – superficial spreading type
. This neoplasm is characterized by asymmetry, scalloped borders, a combinat
ion of various colors and an ulcerated nodule.
114FF9.jpg|Fig. 114.9 Melanoma with regression. Note asymmetr
y, variegation in color and uneven surface. The lighter zones are evidence of re
gression.
114FF10.jpg|Fig. 114.10 Amelanotic melanoma. Hypopigmented er
ythematous patch with focally pigmented margin.
114FF11.jpg|Fig. 114.11 Melanoma – nodular type. A Blac
k nodule on the nose. Courtesy Ron Rapini M.D. B This lesion is technical
ly classified as a nodular component of superficial spreading melanoma because o
f the adjacent flat tan-brown intraepidermal component (radial growth phase) ext
ending beyond the nodule.
114FF12.jpg|Fig. 114.12 Melanoma - lentigo maligna type on sun-da
maged skin. The neoplasm is broad and flat, asymmetrical, poorly circumscrib
ed and shows various shades of tan-brown to black.
114FF13.jpg|Fig. 114.13 Acral lentiginous melanoma. A Extensi
ve centrifugal spread, illustrating the macular character, irregular shape, poor
circumscription, variations in color, reticulation, and whitish area of regress
ion. B This lesion on the toe could be mistaken for a traumatically-induc
ed injury. Courtesy Ron Rapini, M.D.
114FF14.jpg|Fig. 114.14 Melanoma in situ of the nail.
Darkly pigmented band in the nail bed and matrix.
114FF15.jpg|Fig. 114.15 Subungual melanoma. Ulcerated nodule
with destruction of the nail.
114FF16.jpg|Fig. 114.16 Nevoid melanoma. The patient develope
d metastases from this red-brown plaque.
114FF17.jpg|Fig. 114.17 Histopathology of melanoma mimicking Spit
z nevus. This neoplasm could be misdiagnosed as a Spitz nevus because the le
sion is symmetrical and well-circumscribed. This is a melanoma because: nests of
melanocytes have become confluent with formation of sheets; there is no distinc
t maturation of melanocytes; nuclei of melanocytes are atypical and melanocytes
are in mitosis, also at the base of the neoplasm.
114FF18.jpg|Fig. 114.18 Melanoma in association with blue nevus (
malignant blue nevus). Satellite metastases at the periphery.
114FF19.jpg|Fig. 114.19 Histopathology of desmoplastic malignant
melanoma. A Loosely textured spindle cells in focally fibroblastic stroma. I
n the epidermis there are changes of melanoma in situ with proliferation of atyp
ical melanocytes. Note lymphoid infiltrates. B Positive S-100 spindle cel
ls within the dermis.
114FF20.jpg|Fig. 114.20 Ciliary body melanoma.
114FF21.jpg|Fig. 114.21 Black heel. Traumatically induced sub
corneal hematoma simulating acral melanoma.
114FF22.jpg|Fig. 114.22 Dermatoscopy. This pair of images fro
m an invasive malignant melanoma illustrates the clinical pictures (A) an
d the same lesion viewed with dermatoscopy (B). Note the multicomponent p
attern with an atypical pigment network, black dots, irregular streaks, focally
a blue-whitish veiland a white regression zone with hairpin vessels. All these d
ermatoscopic criteria are suggestive of a melanoma.
114FF23.jpg|Fig. 114.23 Pathology of melanoma in situ.
Increased number of melanocytes with atypical nuclei not only in the basal zone
, but also at the upper levels of the epidermis.
114FF24.jpg|Fig. 114.24 Pathology of melanoma. Pagetoid melan
ocytes organized as solitary units and nests varying in size and shape are prese
nt throughout the entire epidermis. Neoplastic melanocytes extend into the dermi
s. Absence of maturation at deeper levels of the dermis.
114FF25.jpg|Fig. 114.25 Pathology of melanoma in situ on s
un-exposed surfaces. Atypical melanocytes both singly and in small nests wit
hin the epidermis and along the follicular epithelium.
114FF26.jpg|Fig. 114.26 Melanoma in situ on the plantar su
rface of a foot. Atypical melanocytes are scattered throughout the hyperplas
tic epidermis including the horny layer. Note dendritic melanocytes.
114FF27.jpg|Fig. 114.27 Microstaging of malignant melanoma. B
reslow's method: measure from the granular layer of the epidermis to the deepest
part of the tumor.
114FF28.jpg|Fig. 114.28 Fifteen-year survival curves comparing di
fferent melanoma stages. Survival of localized melanoma (stage I and II), re
gional metastases (stage III) and distant metastases (stage IV) are compared. Th
e numbers in parentheses are patients from the AJCC melanoma staging database us
ed to calculate the survival rates. The differences between the curves are signi
ficant (p <0.05). Reproduced from Balch et al. Journal of Clinical On
cology 19:3635–3648.
114FF29.jpg|Fig. 114.29 Recurrent melanoma with metastases.
114FF30.jpg|Fig. 114.30 Sentinel lymph node biopsy. Localizat
ion of sentinel lymph node by lymphoscintigraphy: A small incisional biop
sy identifies blue sentinel node; B confirmation with handheld gamma coun
ter. Courtesy of M. Hess and W. Künzi, University Hospital Zürich.
114FT1.jpg|Table 114.1 Risk factors for the development of melano
ma.
114FT2.jpg|Table 114.2 Different types of malignant melanoma.
114FT3.jpg|Table 114.3 Melanocytic lesions that simulate melanoma
s clinically and/or histopathologically39. *These are not melanoc
ytic diseases strictu sensu.
114FT4.jpg|Table 114.4 Non-melanocytic simulators of melanoma39.
114FT5.jpg|Table 114.5 Dermatoscopic criteria and their correspon
ding histopathological features. With permission from Argenziano & Soyer
46, Lancet Oncology 2:443–9. © 2001 Elsevier.
114FT6.jpg|Table 114.6 Criteria for histopathologic diagnosis of
malignant melanoma. Adapted from Ackerman et al51.
114FT7.jpg|Table 114.7 Histopathological reporting of cutaneous m
elanoma. The World Health Organization has recommended notation of radial or
vertical growth phase.
114FT8.jpg|Table 114.8 Proposed stage groupings for cutaneous mel
anoma. Modified from Balch et al63. *Approximate five-year surviv
al in percent, modified from Balch et al57. †Clinica
l staging includes microstaging of the primary melanoma and clinical/radiologic
evaluation for metastases. By convention, it should be used after complete excis
ion of the primary melanoma with clinical assessment for regional and distant me
tastases. ‡Pathologic staging includes microstaging of the prim
ary melanoma and pathologic information about the regional lymph nodes after par
tial or complete lymphadenectomy. Pathologic stage 0 or stage IA patients are th
e exception. #There are no stage III subgroups for clinical staging.
114FT9.jpg|Table 114.9 Melanoma TNM classification. Adapted f
rom Balch et al57. *Micrometastasis are diagnosed after sentinel or e
lective lymphadenectomy. †Macrometastases are defined as clinic
ally detectable nodal metastases confirmed by therapeutic lymphadenectomy or whe

n nodal metastasis exhibits gross extracapsular extension.
114FT10.jpg|Table 114.10 Major independent prognostic factors of
survival in multivariate analyses63.
114FT11.jpg|Table 114.11 Surgical treatment of primary melanoma.
114FT12.jpg|Table 114.12 Completed trials for adjuvant interferon
-α2 therapy in melanoma. RFS, relapse-free survival; +, stat
istically significant; –, statistically insignificant; wk, weeks; t.i.w.,
three times per week; MU, million units; IM, intramuscular; IV, intravenous; SC,
subcutaneous; ECOG, Eastern Cooperative Oncology Group; NCCTG, North Central Ca
ncer Treatment Group; mo, months; HDI, high-dose interferon; LDI, low-dose inter
feron; GMK, GM2 ganglioside, keyhole limpet hemocyanin plus OS21 adjuvant; OS, o
verall survival.
114FT13.jpg|Table 114.13 Symptoms and diagnostic tests for metast
atic melanoma. *Always include thorough medical history and physical investi
gation as well as complete blood count and blood chemistry including LDH. Specia
l procedures such as FDG-PET investigation as well as detection of soluble melan
oma markers (e.g. S-100, MIA) are performed at selected melanoma referral center
s for increased sensitivity of metastasis detection as part of controlled studie
s.
114FT14.jpg|Table 114.14 Treatment options for metastatic melanom
a. *Should be performed as part of controlled studies.
115FF1.jpg|Fig. 115.1 Selected vascular neoplasm associations.
115FF2.jpg|Fig. 115.2 Papillary endothelial hyperplasia. Thro
mbus in blood vessel reorganizing within lumina within papillary projections. Co
urtesy of Ron Rapini, M.D.
115FF3.jpg|Fig. 115.3 Papillary endothelial hyperplasia. Netw
ork of lumina with papillary projections. Courtesy of Ron Rapini, M.D.
115FF4.jpg|Fig. 115.4 Microvenular hemangioma. Slit-like vasc
ular spaces. Courtesy of Ron Rapini, M.D.
115FF5.jpg|Fig. 115.5 Angiolymphoid hyperplasia eosinophilia.
It is usually located on or near the scalp.
115FF6.jpg|Fig. 115.6 Angiolymphoid hyperplasia with eosinophilia
. Cobblestone or hobnail endothelial cells prominently bulge into the lumen
of the vessel, surrounded by lymphocytes and eosinophils. Courtesy of Ron Rapini
, M.D.
115FF7.jpg|Fig. 115.7 Spindle cell hemangioma. Multifocal nod
ularity is typical.
115FF8.jpg|Fig. 115.8 Pyogenic granuloma. Sessile oozing papu
le on the finger, a common site.
115FF9.jpg|Fig. 115.9 Pyogenic granuloma. Pedunculated papule
on the finger.
115FF10.jpg|Fig. 115.10 Pyogenic granuloma. Grouped red papul
es on the lip, a common site.
115FF11.jpg|Fig. 115.11 Pyogenic granuloma. Granulation tissu
e is often grouped into lobules, hence the synonym lobular capillary hemangioma.
The lesion is often clutched by a collarette of epidermis and the stroma is pal
e. Courtesy Ron Rapini MD.
115FF12.jpg|Fig. 115.12 Cherry hemangioma on the back of an adult
. The freckles were related to his neurofibromatosis. Courtesy of Ron Rapini
, M.D.
115FF13.jpg|Fig. 115.13 Hobnail hemangioma (targetoid hemosiderot
ic hemangioma). Courtesy of Ron Rapini, M.D.
115FF14.jpg|Fig. 115.14 Hobnail hemangioma. Superficial dilat
ed blood vessels lined by hobnail endothelial cells, blending with slit-like vac
ular spaces. Courtesy of Ron Rapini, M.D.
115FF15.jpg|Fig. 115.15 Tufted hemangioma. Mottled red macule
s are typical.
115FF16.jpg|Fig. 115.16 Classic Kaposi's sarcoma. Red macules

and plaques of the foot.
115FF17.jpg|Fig. 115.17 Classic Kaposi's sarcoma. Red plaques
of the foot.
115FF18.jpg|Fig. 115.18 Kaposi's sarcoma in a patient with AIDS. Red-brown papules or nodules are often oval to lanceolate.
115FF19.jpg|Fig. 115.19 Kaposi's sarcoma. Patch stage with sl
it-like vascular spaces. Courtesy of Ron Rapini, M.D.
115FF20.jpg|Fig. 115.20 Kaposi's sarcoma. Firm tumor nodule w
ith dilated blood vessels and solid areas of bland spindle cells, slit-like spac
es, and hemorrhage. Courtesy of Ron Rapini, M.D.
115FF21.jpg|Fig. 115.21 Angiosarcoma. Note the tumor mass beh
ind the ear and the widespread purple discoloration elsewhere. Courtesy of Profe
ssor D Burrows, Royal Victoria Hospital, Belfast, UK. Published with permission
from McKee P, Pathology of the skin. © Elsevier Science, 1996.
115FF22.jpg|Fig. 115.22 Angiosarcoma (lymphangiosarcoma). Gro
uped papules on the edematous arm of a woman with Stewart-Treves syndrome. Court
esy of Ron Rapini, M.D.
115FF23.jpg|Fig. 115.23 Angiosarcoma. Infiltration of the der
mis by ill-defined vascular spaces and hyperchromatic, atypical endothelial cell
s. Courtesy of Ron Rapini, M.D.
115FF24.jpg|Fig. 115.24 Glomus tumor presenting with pain and ill
-defined subungual erythema. Courtesy of Ron Rapini, M.D.
115FF25.jpg|Fig. 115.25 Multiple glomangiomas.
115FF26.jpg|Fig. 115.26 Multiple glomangiomas.
115FF27.jpg|Fig. 115.27 Glomus tumor. Glomus cells are monoto
nously rounded and sometimes arranged in a single-file manner. Courtesy of Ron R
apini, M.D.
115FT1.jpg|Table 115.1 A working classification of vascular tumor
s and anomalies. *Covered in this chapter.
116FF1.jpg|Fig. 116.1 The structure and components of the periphe
ral nerve.
116FF2.jpg|Fig. 116.2 Cutaneous neural neoplasms. Histologica
l differential diagnosis. DF, dermatofibroma; DFSP, dermatofibrosarcoma protuber
ans; EMA, epithelial membrane antigen; FXIIIa, Factor XIII antigen; HMB, HMB-45
melanocyte related antibody NF, neural filament; S-100, S-100 protein; SMSA, smo
oth musclespecific actin; +, positive; −, negative.
116FF3.jpg|Fig. 116.3 Traumatic neuroma. Presenting as a pain
ful, firm papule after a deep puncture injury.
116FF4.jpg|Fig. 116.4 Amputation neuroma Polypoid lesion. Not
e the proliferation of nerve fascicles in the fibrotic stroma, and the lack of b
ony structures.
116FF5.jpg|Fig. 116.5 Traumatic neuroma. The chaotic prolifer
ation of nerve fascicles is embedded in a fibrous stroma.
116FF6.jpg|Fig. 116.6 Palisaded encapsulated neuroma. The wel
l-circumscribed dermal nodule appears encapsulated.
116FF7.jpg|Fig. 116.7 Solitary schwannoma. Subcutaneous skin
colored nodule on the finger.
116FF8.jpg|Fig. 116.8 Solitary cutaneous schwannoma. Hypercel
lular areas often show nuclear palisading and Verocay bodies.
116FF9.jpg|Fig. 116.9 Plexiform neurofibroma in a child with neur
ofibromatosis. Bag-like mass with overlying patches of hyperpigmentation.
116FF10.jpg|Fig. 116.10 Neurofibroma. The tumor contains diff
use proliferation of spindle cells with slender, ovoid nuclei in a fibrillary ma
trix.
116FF11.jpg|Fig. 116.11 Plexiform neurofibroma showing irregularl
y expanded, twisted nerve fascicles.
116FF12.jpg|Fig. 116.12 Cellular neurothekeoma of the scalp, pres
enting as an erythematous, firm papule.
116FF13.jpg|Fig. 116.13 Nerve sheath myxoma, classic type. We
ll-defined fascicles with myxoid stroma.

116FF14.jpg|Fig. 116.14 Nerve sheath myxoma, cellular type or cel
lular neurothekeoma. A Epithelioid nests are dispersed in a hyalinized strom
a. B Whorl-like arrangement of epithelioid cells showing nuclear pleomorp
hism and rare mitotic figures.
116FF15.jpg|Fig. 116.15 Granular cell tumor. The tumor may sh
ow a nodular or infiltrative growth pattern. The large polygonal cells have fine
ly granular cytoplasm and round nuclei.
116FF16.jpg|Fig. 116.16 Malignant peripheral nerve sheath tumor.
A The tumor is composed of intersecting fascicles creating a ‘herring
bone’ pattern. B Marked cellular pleomorphism with cytologic atypia
and mitotic activity.
116FF17.jpg|Fig. 116.17 Merkel cell carcinoma (primary neuroendoc
rine carcinoma) presenting as a rapidly growing, violaceous nodule on the toe.
116FF18.jpg|Fig. 116.18 Primary neuroendocrine carcinoma of the s
kin (Merkel cell carcinoma). A Dermal nodule with infiltrating borders. B
 Anaplastic tumor cells with round to ovoid shape, scant nuclei, and fine ch
romatin pattern. C Biopsies of Merkel cell carcinoma stained for certain
keratins, such as keratin-20, have a characteristic perinuclear dot pattern. Cou
rtesy of Ron Rapini, M.D.
116FF19.jpg|Fig. 116.19 Nasal glioma in a newborn. Pink viola
ceous soft nodule.
116FF20.jpg|Fig. 116.20 Neuroblastoma. Clinical manifestation
of a cutaneous metastasis of neuroblastoma in a child. Violaceous, blanchable,
dermal nodule on abdomen.
116FF21.jpg|Fig. 116.21 Cutaneous neuroblastoma. The tumor is
composed of small cells with small, round to ovoid nuclei that can be arranged
in rosettes. The fibrillary material in the center of Homer Wright type rosettes
is characteristic.
116FT1.jpg|Table 116.1 Classification of cutaneous neural tumors.

116FT2.jpg|Table 116.2 Clinical features of benign neural neoplas
ms. NA, not applicable; MEN 2B, multiple endocrine neoplasia, type 2B.
116FT3.jpg|Table 116.3 Histologic differential diagnostic feature
s of common cutaneous neural neoplasms.
116FT4.jpg|Table 116.4 Tumors and tumor-like conditions of ectopi
c and heterotopic neural tissue involving the skin.
117FF1.jpg|Fig. 117.1 Infarcted skin tag. A pedunculated dark
-red papule in the axilla. (Courtesy of the Ronald O Perelman Department of Derm
atology, New York University.)
117FF2.jpg|Fig. 117.2 Fibrous papule of the nose. A smooth, d
ome-shaped, skin-colored papule on the nose. Courtesy of the Ronald O Perelman,
M.D., Department of Dermatology, New York University.
117FF3.jpg|Fig. 117.3 Pearly penile papules. Multiple small w
hite papules along the corona of the glans penis. Note the multilayered distribu
tion. Courtesy Kalman Watsky, M.D.
117FF4.jpg|Fig. 117.4 Facial angiofibromas of tuberous sclerosis.
 There are multiple firm papules of the nose and cheek. Courtesy of the Rona
ld O Perelman, M.D., Department of Dermatology, New York University.
117FF5.jpg|Fig. 117.5 Angiofibroma. There is dermal fibroplas
ia with dilated thin-walled vessels and large stellate fibroblasts.
117FF6.jpg|Fig. 117.6 Dermatofibroma. Hyperpigmented firm pap
ules on the lower extremity. Courtesy of Jean Bolognia, M.D.
117FF7.jpg|Fig. 117.7 Dermatofibroma. There is a nodular prol
iferation of spindled fibroblasts and histiocytes in the reticular dermis, with
hyperplasia and hyperpigmentation of the overlying epidermis. There is extension
into the subcutaneous tissue in a radial pattern (arrow).
117FF8.jpg|Fig. 117.8 Dermatofibroma. The fibroblasts are arr
anged in broad intersecting fascicles with entrapment of thick collagen bundles.
117FF9.jpg|Fig. 117.9 Differentiating dermatofibroma (DF) and der

matofibrosarcoma protruberans (DFSP).
117FF10.jpg|Fig. 117.10 Dermatofibroma with atypical cells. T
here are histiocyte-like cells with large hyperchromatic nuclei and scattered fi
broblasts.
117FF11.jpg|Fig. 117.11 Acral fibrokeratoma. A pink exophytic
papule arising from the dorsal surface of the finger. Courtesy of the Ronald O
Perelman, M.D., Department of Dermatology, New York University.
117FF12.jpg|Fig. 117.12 Acral fibrokeratoma. There is a digit
ated fibrovascular core with vertically arranged collagen bundles lined by epide
rmal hyperplasia. Note the thick stratum corneum.
117FF13.jpg|Fig. 117.13 Sclerotic fibroma. The collagen bundl
es in this hypocellular tumor are arranged in short parallel bundles, leading to
a laminated or ‘plywood’ appearance.
117FF14.jpg|Fig. 117.14 Pleomorphic fibroma. There are interw
oven coarse collagen bundles with a few interspersed large mono- and multinuclea
ted atypical fibroblasts.
117FF15.jpg|Fig. 117.15 Multinucleate cell angiohistocytoma.
Grouped erythematous macules and papules on the thigh. Hemorrhagic crust represe
nts biopsy site. Courtesy of the Ronald O Perelman, M.D., Department of Dermatol
ogy, New York University.
117FF16.jpg|Fig. 117.16 Multinucleate cell angiohistocytoma.
There is a proliferation of thin-walled, dilated blood vessels and multinucleate
d giant cells. The fibrous stroma is more delicate than that seen in angiofibrom
as.
117FF17.jpg|Fig. 117.17 Dermatomyofibroma. The myofibroblasts
are arranged in long intersecting fascicles that are parallel to the skin surfa
ce.
117FF18.jpg|Fig. 117.18 Giant cell tumor of the tendon sheath. A skin-colored nodule on the lateral aspect of the index finger. Courtesy of t
he Ronald O Perelman, M.D., Department of Dermatology, New York University.
117FF19.jpg|Fig. 117.19 Giant cell tumor of the tendon sheath. The tumor is composed of sheets of epithelioid histiocytes with a variable num
ber of the characteristic multinucleated osteoclast-like giant cells. Some of th
e histiocytes may have pale foamy cytoplasm. (Courtesy of Dr Jacqueline M Wharto
n.).
117FF20.jpg|Fig. 117.20 Nodular fasciitis. Spindle-shaped and
stellate fibroblasts are loosely arranged in a myxomatous stroma, with some cel
ls in mitosis.
117FF21.jpg|Fig. 117.21 Infantile digital fibroma. Firm skincolored nodule on the dorsolateral aspect of the second toe in a young child.
117FF22.jpg|Fig. 117.22 Infantile digital fibroma. Myofibrobl
asts have pathognomonic cytoplasmic eosinophilic hyalin globules (arrows).
117FF23.jpg|Fig. 117.23 Infantile myofibromatosis. Multiple f
irm violaceous papulonodules on the scalp. Courtesy of Yale Residents Slide Coll
ection.
117FF24.jpg|Fig. 117.24 Calcifying aponeurotic fibroma. Islan
ds of calcification are surrounded by palisaded and osteoclast-like fibroblasts.
In between these areas are sheets of spindled and epithelioid fibroblasts in a
collagenous stroma.
117FF25.jpg|Fig. 117.25 Fibrous hamartoma of infancy. It is c
omposed of a mixture of elongated bundles of spindle-shaped myofibroblasts, clus
ters of smaller immature mesenchymal cells in a myxoid stroma, and mature adipoc
ytes.
117FF26.jpg|Fig. 117.26 Knuckle pads. Note the localization t
o the skin overlying the knuckles. Courtesy Dr Ronald P Rapini, M.D.
117FF27.jpg|Fig. 117.27 Fibromatosis. Slender spindle-shaped
fibroblasts and collagen strands are arranged in broad sweeping fascicles.
117FF28.jpg|Fig. 117.28 Connective tissue nevus. Coalescence
of multiple tan papules and plaques on the lower back. The lesion was firm to pa
lpation and histologically had increased collagen.

117FF29.jpg|Fig. 117.29 Osteopoikilosis. In this radiograph,
multiple asymptomatic round to oval areas of increased bone density are seen in
the tibia. Courtesy of Jean Bolognia, M.D.
117FF30.jpg|Fig. 117.30 Atypical fibroxanthoma. A crusted pin
k nodule on the external ear of an elderly man.
117FF31.jpg|Fig. 117.31 Atypical fibroxanthoma. The spindle c
ells have pale foamy cytoplasm and hyperchromatic nuclei with small nucleoli. Th
ere is also a large atypical giant cell with darker nuclear chromatin as well as
a cell in atypical mitosis.
117FF32.jpg|Fig. 117.32 Dermatofibrosarcoma protuberans. A br
oad red-brown plaque on the abdomen, with several superimposed nodules. Courtesy
of the Ronald O. Perelman, M.D., Department of Dermatology, New York University
.
117FF33.jpg|Fig. 117.33 Dermatofibrosarcoma protuberans, plaque s
tage. Characteristic multilayered pattern of infiltration into the subcutane
ous tissue.
117FF34.jpg|Fig. 117.34 Dermatofibrosarcoma protuberans. The
spindle-shaped cells are arranged in a ‘storiform’ pattern.
117FF35.jpg|Fig. 117.35 Dermatofibrosarcoma protuberans, nodular
stage. At the base of the tumor, the neoplastic cells infiltrate the subcuta
neous tissue to produce a honeycomb pattern.
117FF36.jpg|Fig. 117.36 Giant cell fibroblastoma. This pseudo
vascular or ‘angiectoid’ space lined by giant cells with hyperchroma
tic nuclei is characteristic of this tumor.
117FF37.jpg|Fig. 117.37 Fibrosarcoma. Cellular fascicles of a
typical spindle-shaped fibroblasts with coarse nuclear chromatin are arranged in
a ‘herringbone’ pattern.
117FF38.jpg|Fig. 117.38 Epithelioid sarcoma. The atypical epi
thelioid cells are palisaded around an area of necrosis. Courtesy of Jacqueline
M Wharton, M.D.
117FT1.jpg|Table 117.1 Histologic variants of dermatofibroma.
118FF1.jpg|Fig. 118.1 Evaluation of muscle, adipose and cartilage
tumors. Courtesy of Yale Residents Slide Collection.
118FF2.jpg|Fig. 118.2 Grouped leiomyomata of the back. Courte
sy of Yale Residents Slide Collection.
118FF3.jpg|Fig. 118.3 Myocytes of a smooth muscle tumor. A Th
ey are at least focally arranged in intersecting fascicles. B At higher m
agnification the cells have eosinophilic cytoplasm and elongated nuclei with rou
nded ends.
118FF4.jpg|Fig. 118.4 Piloleiomyoma. A Piloleiomyoma centered
in the reticular dermis forming a nodule with fascicles of myocytes interdigita
ting between collagen bundles at its periphery. B The center of the lesio
n shows intersecting fascicles of smooth muscle cells.
118FF5.jpg|Fig. 118.5 Angioleiomyoma. A Angioleiomyomas are w
ell circumscribed and often located in the deep dermis, extending into the subcu
tis. B At higher magnification thick-walled vessels are surrounded by bun
dles of smooth muscle cells.
118FF6.jpg|Fig. 118.6 Leiomyosarcoma. A A large tumor extendi
ng from upper reticular dermis deep into the subcutis. B At higher magnif
ication this neoplasm is more cellular than a leiomyoma. The nuclei are pleomorp
hic, more hyperchromatic and have coarse chromatin. C Mitotic figures are
numerous and are easily identified.
118FF7.jpg|Fig. 118.7 Smooth muscle hamartoma. This infant pr
esented with a firm plaque on the thigh. Courtesy of Ron Rapini, MD.
118FF8.jpg|Fig. 118.8 In familial multiple lipomatosis several di
screte lipomas are present on the forearm. Courtesy of Yale Residents Slide
Collection.
118FF9.jpg|Fig. 118.9 Lipomas. They are composed of a uniform
population of mature fat cells with small and eccentric nuclei.
118FF10.jpg|Fig. 118.10 Angiolipoma. A In angiolipomas, matur

e fat is admixed with a variable number of small vessels. B Occasional ve
ssels are occluded by fibrin thrombi.
118FF11.jpg|Fig. 118.11 Spindle cell lipoma. A This low power
photomicrograph shows all three components of a spindle cell lipoma – spi
ndle cells, mature fat cells and ropey collagen. B The spindle cells are
small, uniform, bland and have inconspicuous cytoplasm. C High magnificat
ion of thick, ‘ropey’ collagen.
118FF12.jpg|Fig. 118.12 Hibernoma. A Hibernoma with character
istic lobulation. B The cytoplasm of hibernoma cells ranges from multivac
uolated to granular.
118FF13.jpg|Fig. 118.13 Nevus lipomatosus superficialis. A Th
is hamartoma is characterized by grouped soft, pedunculated skin-colored tumors;
a partial resection had been performed. B Histopathologically, mature fa
t cells seen in the dermis are pathognomonic.
118FF14.jpg|Fig. 118.14 Liposarcoma. Note the large mass in t
he right buttock. Courtesy of Ron Rapini, M.D.
118FF15.jpg|Fig. 118.15 Liposarcoma. Lipoblasts are immature
fat cells, with a hyperchromatic nucleus that is scalloped by cytoplasmic fat va
cuoles. Their presence is mandatory for a diagnosis of liposarcoma. Courtesy of
Richard Kempson, M.D.
118FF16.jpg|Fig. 118.16 The varied histopathologic features of li
posarcoma. A Myxoid liposarcoma – without the clinical context this tu
mor can be indistinguishable from lipoblastoma. Bland spindle cells occur in a m
yxoid matrix with plexiform vessels. B Pleomorphic liposarcoma – an
aplastic and cellular neoplasm. Lipoblasts may be difficult to find.
118FT1.jpg|Table 118.1 Special stains to confirm smooth muscle di
fferentiation
118FT2.jpg|Table 118.2 Immunohistochemical findings in leiomyosar
coma relative to other spindle cell tumors (AFX, atypical fibroxanthoma; MFH, ma
lignant fibrous histiocytoma; SCC, spindle cell squamous carcinoma)
119FF1.jpg|Fig. 119.1 Differences in clinical presentations and c
ourse of childhood and adult onset mastocytosis. The mechanism responsible f
or most cases of childhood mastocytosis differs from adult onset disease.
119FF2.jpg|Fig. 119.2 Mast cell mediators and associated symptoms
of mastocytosis. (PGD2, prostaglandin D2; LT, leukotrienes; PAF, platelet a
ctivating factor; TNF, tumor necrosis factor; IL, interleukins; SCF, stem cell f
actor.)
119FF3.jpg|Fig. 119.3 A mastocytoma in an infant.
119FF4.jpg|Fig. 119.4 Typical lesions of urticaria pigmentosa in
a child.
119FF5.jpg|Fig. 119.5 Spontaneous blister in an infant with diffu
se cutaneous mastocytosis.
119FF6.jpg|Fig. 119.6 Typical reddish-brown papules of adult mast
ocytosis.
119FF7.jpg|Fig. 119.7 Telangiectasia eruptiva maculans perstans. The mixture of telangiectasia and hyperpigmentation is evident in this photo
graph.
119FF8.jpg|Fig. 119.8 Darier's sign in an adult with diffuse urti
caria pigmentosa. Courtesy of Thomas Horn MD.
119FF9.jpg|Fig. 119.9 Mast cells have a ‘fried egg’ a
ppearance with granules in the amphophilic cytoplasm.
119FF10.jpg|Fig. 119.10 When the Leder method utilizing naphthol
AS-D chloroacetate esterase is employed, the mast cell granules appear red.
119FT1.jpg|Table 119.1 Classification of mastocytosis.
119FT2.jpg|Table 119.2 Therapeutic ladder for mastocytosis.
120FF1.jpg|Fig. 120.1 Cutaneous follicle center cell lymphoma. Large ulcerated tumors on the scalp surrounded by infiltrated erythematous nod
ules and plaques.
120FF2.jpg|Fig. 120.2 Cutaneous follicle center cell lymphoma. Large ulcerated tumor on the back. Note surrounding erythematous papules, patc
hes and plaques.
120FF3.jpg|Fig. 120.3 Cutaneous marginal zone B-cell lymphoma. Solitary, large erythematous nodule on the upper arm.
120FF4.jpg|Fig. 120.4 Cutaneous marginal zone B-cell lymphoma. Multiple erythematous papules on the arm.
120FF5.jpg|Fig. 120.5 Cutaneous immunocytoma. Domeshaped eryt
hematous nodule with smooth surface. The surrounding area shows features of acro
dermatitis chronica atrophicans.
120FF6.jpg|Fig. 120.6 Cutaneous large B-cell lymphoma of the leg.
 Multiple redbrown tumors on the lower leg.
120FF7.jpg|Fig. 120.7 Cutaneous B-cell lymphoblastic lymphoma. Large erythematous tumor on the scalp of an 11-month-old child.
120FF8.jpg|Fig. 120.8 Cutaneous follicle center cell lymphoma, di
ffuse type. A Diffuse infiltrate without follicular pattern. B
Centroblasts and medium and large-sized centrocytes predominate.
120FF9.jpg|Fig. 120.9 Cutaneous follicle center cell lymphoma, folli
cular type. Neoplastic follicles with monomorphous morphology.
120FF10.jpg|Fig. 120.10 Pattern of immunoglobulin light chain exp
ression.
120FF11.jpg|Fig. 120.11 Cutaneous marginal zone B-cell lymphoma. A Small nodules of reactive lymphocytes (dark areas) surrounded by neoplasti
c marginal zone cells, lymphoplasmacytoid cells, and plasma cells (clear areas).
B Monotypic expression of lambda immunoglobulin light chain within the neoplast
ic population of cells.
120FF12.jpg|Fig. 120.12 Cutaneous large B-cell lymphoma of the le
g. Large cells with a round morphology (mainly immunoblasts) predominate.
120FF13.jpg|Fig. 120.13 Cutaneous plasmacytoma. Plasma cells,
some with atypical nuclei, predominate.
120FF14.jpg|Fig. 120.14 Cutaneous intravascular B-cell lymphoma. Intravascular proliferation of medium to large-sized atypical lymphocytes.
120FF15.jpg|Fig. 120.15 Cutaneous B-lymphoblastic lymphoma. M
edium-sized blasts with the characteristic ‘mosaic-stone’ linear arr
angement.
120FF16.jpg|Fig. 120.16 Evaluation of the patient with a suspecte
d diagnosis of cutaneous B-cell lymphoma.
120FT1.jpg|Table 120.1 Classification of primary cutaneous B-cell
lymphoma according to the EORTC and corresponding categories in the WHO classif
ication. EORTC, European Organization for Research and Treatment of Cancer;
WHO, World Health Organization.
120FT2.jpg|Table 120.2 Antibodies useful in the immunohistologica
l analysis of primary cutaneous B-cell lymphomas. The antibodies are general
ly used with routinely fixed, paraffin-embedded sections of tissue.
120FT3.jpg|Table 120.3 Cutaneous manifestations of a monoclonal g
ammopathy.
121FF1.jpg|Fig. 121.1 Algorithm for the classification of cutaneo
us T-cell lymphoma. Adapted from reference 12.
121FF2.jpg|Fig. 121.2 Mycosis fungoides, limited patch/plaque sta
ge disease (stage 1A). A Patches on the buttocks involving less than 10% of
the skin surface. B Atypical lymphocytes in a typical linear configuratio
n along the epidermal basal layer.
121FF3.jpg|Fig. 121.3 Mycosis fungoides, generalized patch/plaque
stage disease (stage 1B). A Extensive patches and plaques involving more th
an 10% of the skin surface. B Pronounced epidermotropism with the formati
on of small nests of atypical cells (Pautrier's microabscesses).
121FF4.jpg|Fig. 121.4 Mycosis fungoides, tumor stage. A Multi
ple skin tumors in combination with typical patches and plaques. B Diffus
e dermal infiltrates of mediumsized to large neoplastic T cells.
121FF5.jpg|Fig. 121.5 Follicular mycosis fungoides. A Infiltr
ated plaques on the forehead and eyebrow with concurrent hair loss. B Cha
racteristic perifollicular infiltrates with extensive follicular mucinosis (aste

risks). Note absence of epidermotropism.
121FF6.jpg|Fig. 121.6 Pagetoid reticulosis. A Solitary plaque
on the left upper leg. B Purely intraepidermal proliferation of atypical
T cells.
121FF7.jpg|Fig. 121.7 Granulomatous slack skin. Pendulous fol
d of atrophic lax skin in the right inguinal area.
121FF8.jpg|Fig. 121.8 Sézary's syndrome. Electron photom
icrograph of a skin biopsy showing characteristic Sézary cells.
121FF9.jpg|Fig. 121.9 Sézary's syndrome. Erythroderma.
121FF10.jpg|Fig. 121.10 Algorithm for the diagnosis and treatment
of primary cutaneous CD30-positive lymphoproliferations52.
121FF11.jpg|Fig. 121.11 Primary cutaneous CD30-positive large T-c
ell lymphoma. A Characteristic clinical presentation with a solitary ulcerat
ing tumor. B Detail of dermal infiltrate showing cohesive clusters of lar
ge (CD30-positive) anaplastic cells with pronounced eosinophilic nucleoli and ab
undant cytoplasm.
121FF12.jpg|Fig. 121.12 Lymphomatoid papulosis. A Clinical pr
esentation with papulonecrotic skin lesions at different stages of evolution. B Detail of dermal infiltrate showing a mixed inflammatory infiltrate with
scattered (CD30-positive) large anaplastic T cells (LyP, type A).
121FF13.jpg|Fig. 121.13 Primary cutaneous CD30-negative large T-c
ell lymphoma. Rapidly growing nodules and tumors. Note: the skin lesions in
the left upper corner do not represent patches, but rather deep plaques present
for two weeks.
121FF14.jpg|Fig. 121.14 Subcutaneous panniculitis-like T-cell lym
phoma. Subcutaneous infiltrate with characteristic rimming of individual fat
cells by the neoplastic T cells.
121FF15.jpg|Fig. 121.15 Epidermotropic CD8-positive cutaneous T-c
ell lymphoma. Generalized skin tumors with central ulceration. Previously, s
uch cases were designated as disseminated pagetoid reticulosis (Ketron-Goodman t
ype).
121FF16.jpg|Fig. 121.16 Nasal NK/T-cell lymphoma. An extensiv
e ulceronecrotic nasal mass, previously referred to as lethal midline granuloma.
121FF17.jpg|Fig. 121.17 Blastic NK-cell lymphoma. Monotonous
proliferation of medium-sized to large CD3−, CD4+, CD8− tumor cells
showing strong expression of CD56.
121FT1.jpg|Table 121.1 EORTC classification for primary cutaneous
T-cell lymphomas and corresponding categories in the WHO classification. *B
ased on 724 primary CTCL included in the Dutch registry between 1985 and 1999.
121FT2.jpg|Table 121.2 Differential diagnosis of common histologi
c patterns in CTCL. TIA, T-cell restricted intercellular antigen; ALK, anapl
astic lymphoma kinase.
121FT3.jpg|Table 121.3 TNMB classification of mycosis fungoides.
121FT4.jpg|Table 121.4 Clinical staging system for mycosis fungoi
des.
121FT5.jpg|Table 121.5 Treatment of mycosis fungoides. HN2, t
opical nitrogen mustard; RT, local radiotherapy; TSEB, total skin electron beam;
INF, interferon; ECP, extracorporeal photophoresis. *Efficacy compared to tradi
tional treatments yet to be determined.
122FF1.jpg|Fig. 122.1 Lymphocytic infiltrate of Jessner. Annu
lar erythematous plaque on the face. Courtesy of Yale Residents Slide Collection
.
122FF2.jpg|Fig. 122.2 Lymphocytic infiltrate of Jessner. A su
perficial and deep perivascular infiltrate without an interface component are ty
pical.
122FF3.jpg|Fig. 122.3 Differential diagnosis of lymphocytic infil
trate of Jessner.
122FF4.jpg|Fig. 122.4 Cutaneous lymphoid hyperplasia. Erythem
atous nodules are characteristic of this disease.

122FF5.jpg|Fig. 122.5 Cutaneous lymphoid hyperplasia demonstr
ates germinal center formation, the presence of tingible-body macrophages, and a
mantle zone.
122FF6.jpg|Fig. 122.6 Leukemia cutis. Multiple erythematous p
apules and plaques in a patient with hairy cell leukemia. Courtesy of Yale Resid
ents Slide Collection.
122FF7.jpg|Fig. 122.7 Chronic lymphocytic leukemia. A Chronic
lymphocytic leukemia infiltrates the skin in a dense and diffuse manner. B The cells in chronic lymphocytic leukemia are strikingly monomorphous and lac
k significant cytologic atypia.
122FF8.jpg|Fig. 122.8 Cutaneous Hodgkin's disease. This may d
isplay characteristic Reed–Sternberg cells (center) amidst a mixed lymphoc
ytic background.
122FT1.jpg|Table 122.1 Microscopic differences between cutaneous
lymphoid hyperplasia (CLH) and cutaneous lymphoma.
122FT2.jpg|Table 122.2 Differential diagnosis of ‘blueberry
muffin baby’.
122FT3.jpg|Table 122.3 ‘Inflammatory’ disorders assoc
iated with acute and chronic leukemias15–18. ALL, acute lym
phoblastic leukemia; AML, acute myelogenous leukemia; AMML, acute myelomonocytic
leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia;
CMML, chronic myelomonocytic leukemia; CNL, chronic neutrophilic leukemia.
123FF1.jpg|Fig. 123.1 Ulcerated erythematous nodules on the anter
ior trunk due to metastases of adenocarcinoma of the lung. Courtesy of Yale
123FF2.jpg|Fig. 123.2 Large ulcerated nodule on the scalp represe
nting a metastasis from a primary lung squamous cell carcinoma. Note the ass
ociated alopecia.
123FF3.jpg|Fig. 123.3 Inflammatory breast cancer of the chest wal
l with cellulitis-like appearance. Markings placed for radiation therapy. Co
urtesy of Yale Residents Slide Collection.
123FF4.jpg|Fig. 123.4 Metastatic breast cancer involving the ches
t and upper arm. The skin is indurated due to fibrosis and has a peau d'oran
ge appearance; this presentation is referred to as ‘en cuirasse’.
 Courtesy of Yale Residents Slide Collection.
123FF5.jpg|Fig. 123.5 Photomicrograph of a cutaneous metastasis o
f breast carcinoma. Note the single-file pattern of the tumor cells.
123FF6.jpg|Fig. 123.6 Approach to cutaneous metastsasis of unknow
n origin. Note: these generalizations are not valid in every case.
123FT1.jpg|Table 123.1 The percentage of patients with metastatic
cancer who had cutaneous metastases. Adapted from Lookingbill et al3

123FT2.jpg|Table 123.2 A ranking of the underlying primary malign
ancies in patients with cutaneous metastases. Adapted from Lookingbill et al3
124FF1.jpg|Fig. 124.1 Age-specific prevalence of one or more sign
ificant skin conditions in a US population. According to Johnson 1978.
124FF2.jpg|Fig. 124.2 The positive predictive value of an allergi
c contact dermatitis (ACD) is a function of the true prevalence of ACD, the patc
h test specificity and the patch test sensitivity.
124FF3.jpg|Fig. 124.3 Selection bias in epidemiological studies o
n skin diseases.
124FF4.jpg|Fig. 124.4 Annual incidence rates of occupational cont
act dermatitis in North Bavaria.
124FT1.jpg|Table 124.1 Descriptive, analytic and intervention der
mato-epidemiology.
124FT2.jpg|Table 124.2 The relevance of epidemiology for dermatol
ogy.
124FT3.jpg|Table 124.3 Inflammatory skin diseases are very common
in the population.
124FT4.jpg|Table 124.4 Skin diseases in a population of 100 000 p
eople over a one-year period9. *Excludes cutaneous neoplasms, vir
al warts, herpes simplex and scabies.
124FT5.jpg|Table 124.5 The number of correct and false-positive p
atch test results according to different prevalence rates of sensitization assum
ing a sensitivity and specificity of 90%. Numbers are given with the assumpt
ion that 1000 patients have been patch tested.
124FT6.jpg|Table 124.6 Statistical significance can be influenced
by sensitivity and specificity. The upper table shows a statistically signi
ficant association between hand eczema and nickel allergy. The lower table shows
the effects of misclassification assuming a sensitivity and specificity of 90%
for patch testing (worst case scenario).
124FT7.jpg|Table 124.7 Sensitivity and specificity of the UK diag
nostic criteria for atopic according to different validation studies.
124FT8.jpg|Table 124.8 A hypothetical example where an increase i
n the prevalence of atopic dermatitis can be explained by a decrease in specific
ity.
124FT9.jpg|Table 124.9 Reasons for systematic errors in samples o
f patients with skin diseases.
124FT10.jpg|Table 124.10 Sick-leave, medical consultation due to
‘work-related’ hand eczema in different occupational groups. Mod
ified according to Smit et al.33
124FT11.jpg|Table 124.11 Age-standardized rates of NMSC in Caucas
ians per 100 000 population from Australia, US and Europe. Selected studies
after 1990, according to Diepgen & Mahler3.
124FT12.jpg|Table 124.12 The hierarchy of evidence.
124FT13.jpg|Table 124.13 The six steps involved in conducting a s
ystematic review.
124FT14.jpg|Table 124.14 Questions to ask when applying the resul
ts of a critical appraisal back to the patient. Modified according to Willli
ams69.
125FF1.jpg|Fig. 125.1 The stratum corneum is a unique two-compart
ment system, analogous to a brick wall. Whereas lipids are sequestered extra
cellularly within the stratum corneum, the corneocyte is lipid-depleted, but pro
tein-enriched.
125FF2.jpg|Fig. 125.2 Lamellar body secretion delivers not only l
ipid precursors, but also several hydrolytic enzymes to the extracellular domain
s. These enzymes both generate the mature lamellar bilayers as well as the d
egradation of corneodesmosomes. Note that these processes, in turn, impact on a
number of important functions beyond the barrier and desquamation.
125FF3.jpg|Fig. 125.3 The degradation of corneodesmosomes. Th
e degradation of corneodesmosomes results in discontinuous lacunar domains, whic
h represent the likely aqueous ‘pore’ pathway. These lacunae can enl
arge and extend, forming a continuous, but collapsible network under certain con
ditions, e.g. prolonged hydration, sonophoresis.
125FF4.jpg|Fig. 125.4 The major synthetic pathways that lead to t
he generation of the three key barrier lipids of the stratum corneum. The ra
te-limiting enzymes in each pathway are shown. Each enzyme, in turn, represents
a potential target for a metabolic intervention to enhance drug delivery (see Fi
g. 125.9).
125FF5.jpg|Fig. 125.5 pH regulates sequential enymatic steps that
lead to formation of mature stratum corneum lamellar membranes. The process
begins at the SG/SC interface.
125FF6.jpg|Fig. 125.6 Theoretical advantages of transdermal deliv
ery include less toxicity and improved efficacy. This is due to a reduction
in the ‘peaks’ and ‘valleys’, associated with bolus ther
apy.
125FF7.jpg|Fig. 125.7 Lipophilic agents (e.g. n-butanol),
penetrate across the stratum corneum (SC) via the intercellular spaces. Note
huge volume expansion of extracellular domains, representing the putative SC re

servoir. Method: n-butanol precipitation in situ with osmiu
m vapors.
125FF8.jpg|Fig. 125.8 After initial barrier perturbations, metabo
lic interventions can delay barrier recovery. This creates an increased pote
ntial, i.e. a ‘window’, for transdermal drug delivery.
125FF9.jpg|Fig. 125.9 Potential metabolic interventions are illus
trated in a vertical display. SC, stratum corneum.
125FF10.jpg|Fig. 125.10 Most metabolic interventions create phase
separation. The formation of non-lamellar domains leads to additional poten
tial pathways for transdermal drug delivery. SC, stratum corneum.
125FF11.jpg|Fig. 125.11 Betamethasone valerate absorption through
human skin in vitro. The same two products were also evaluated clini
cally. A sixfold increase in absorption from a foam product versus a lotion prod
uct resulted in a 50% increase in efficacy in the treatment of scalp psoriasis.
Reproduced from Franz TJ, et al. Betamethasone valerate foam 0.12%: a novel vehi
cle with enhanced delivery and efficacy. Int J Dermatol. 1999;38:628–32.
125FF12.jpg|Fig. 125.12 Lidocaine absorption through human skin in vitro. Incorporation of DMSO as a co-solvent with ethanol results i
n both increased drug solubility (Cv) and partitioning (Km). At 10% drug concentration, the maximum flux is 10-fold greater
than that achieved in an emulsion formulation (eutectic mixture of lidocaine 2.5
% and prilocaine 2.5% (EMLA)). At 1% drug concentration in DMSO the maximum flux
is twofold greater than 2.5% drug in EMLA. Reproduced from Mallory SB, et al. T
opical lidocaine for anesthesia in patients undergoing pulsed dye laser treatmen
t for vascular malformations. Ped Dermatol. 1993;10:370–5.
125FT1.jpg|Table 125.1 Evolving concepts of the stratum corneum.
125FT2.jpg|Table 125.2 How stratum corneum lipids mediate barrier
function.
125FT3.jpg|Table 125.3 Transdermal drug delivery: theoretical adv
antages.
125FT4.jpg|Table 125.4 Transdermal drug delivery: issues with cur
rent approaches.
125FT5.jpg|Table 125.5 Effect of vehicle on potency60,62</su
p>.
126FF1.jpg|Fig. 126.1 Chemical structure of cortisol (hydrocortis
one). Note hydroxyl group at 11 position.
126FF2.jpg|Fig. 126.2 Radiograph of the spine showing severe demi
neralization. This is indicative of advanced osteoporosis.
126FF3.jpg|Fig. 126.3 Radiograph of the head of the femur that fa
ils to demonstrate early stages of osteonecrosis.
126FF4.jpg|Fig. 126.4 Magnetic resonance imaging study of the hea
d of the femur demonstrating osteonecrosis (arrows). (Same patient as in Fig
. 126.3.)
126FF5.jpg|Fig. 126.5 12-year-old female patient treated with int
ermittent systemic GCS for severe atopic dermatitis. Note lens opacity of le
ft eye, indicating development of a cataract.
126FF6.jpg|Fig. 126.6 Striae in a patient on chronic oral prednis
one therapy.
126FF7.jpg|Fig. 126.7 Teenage boy on oral GCS for systemic lupus
erythematosus. Uniform papulopustules of the back typical of a systemic GCSinduced acneiform eruption.
126FF8.jpg|Fig. 126.8 Steroid rosacea due to application of mid-p
otency glucocorticosteroids to the face. Courtesy of Kalman Watsky, M.D.
126FF9.jpg|Fig. 126.9 Local side effects of intralesional glucoco
rticosteroids. Telangiectasias, dermal and subcutaneous atrophy and yellow-w
hite deposits of triaminolone acetonide.Courtesy of Jean Bolognia, M.D.
126FT1.jpg|Table 126.1 Pharmacology of glucocorticosteroids.
126FT2.jpg|Table 126.2 Major indications for the possible use of
systemic glucocorticosteroids in dermatology.

126FT3.jpg|Table 126.3 Potency ranking of some commonly used topi
cal glucocorticosteroids.
126FT4.jpg|Table 126.4 Acute (short-term) side effects of systemi
c glucocorticosteroid therapy
126FT5.jpg|Table 126.5 Major side reactions of long-term systemic
glucocorticosteroid therapy
126FT6.jpg|Table 126.6 Patients at higher risks for toxicity from
glucocorticosteroid therapy
127FF1.jpg|Fig. 127.1 Chemistry of retinoids.
127FF2.jpg|Fig. 127.2 Metabolism and mechanism of action of natur
al retinoids. RE, retinyl esters; RBP, retinol binding protein; CRBP, cellul
ar retinol binding protein; LRAT, lecithin:retinol acyl transferase; ARAT, acylCoA:retinol acyl transferase; REH, retinyl ester hydrolase; RA, retinoic acid; C
RABP, cytosolic retinoic acid binding protein; RAR, retinoic acid receptor; RXR,
retinoid X receptor; VDR, vitamin D3 receptor; TR, thyroid receptor; PPAR, pero
xisome proliferator activated receptor.
127FF3.jpg|Fig. 127.3 Chronic plaque-type psoriasis. Before (
A) and after (B) treatment with a combination of acitretin and pso
ralen plus ultraviolet A (PUVA).
127FF4.jpg|Fig. 127.4 Severe acne vulgaris. Before (A)
and after (B) treatment with oral isotretinoin.
127FF5.jpg|Fig. 127.5 Lamellar ichthyosis. Before (A)
and after (B) treatment with acitretin.
127FF6.jpg|Fig. 127.6 Pityriasis rubra pilaris. Before (A) and after (B) treatment with acitretin.
127FF7.jpg|Fig. 127.7 Cheilitis in an isotretinoin-treated patien
t.
127FF8.jpg|Fig. 127.8 Osteophytes and bony ridges without narrowi
ng of the disk spaces in an acne patient treated with a prolonged course of isot
retinoin.
127FT1.jpg|Table 127.1 Biological functions of retinoids. *Re
tinoic acid can substitute for retinol with regard to growth, morphogenesis and
epithelial differentiation; it cannot substitute completely for retinol in repro
ductive function, nor can it replace retinaldehyde in the visual cycle.
127FT2.jpg|Table 127.2 The key pharmacological features and nucle
ar binding profile of retinoids. *Limited propensity for distribution to sys
temic tissues. **No clearly identified affinity for any retinoid receptor. ***9cis retinoic acid binds both RXR and RAR. ****Increased with food intake, highly
variable.
127FT3.jpg|Table 127.3 Clinical indications of retinoids.
127FT4.jpg|Table 127.4 Various formulations of topical and system
ic retinoids. X, Pregnancy category X; C, pregnancy category C; D, pregnancy
category D. #Under clinical investigation.
127FT5.jpg|Table 127.5 Adverse effects of retinoids. See Tabl
e 127.6 for teratogenicity. *Common adverse effects.
127FT6.jpg|Table 127.6 Retinoid embryopathy.
128FF1.jpg|Fig. 128.1 Sites of action of antibacterial drugs.
This figure illustrates a prototypical bacterial cell. Each class of antibacter
ial drug exerts its effect on a particular component of the cell.
128FF2.jpg|Fig. 128.2 Mechanism of action of sulfonamides and tri
methoprim. Sulfonamides inhibit the conversion of pteridine precursors and P
ABA to folic acid by dihydropteroate synthetase. Trimethoprim inhibits the conve
rsion of dihydrofolate to tetrahydrofolate by dihydrofolate reductase. The end r
esult of both actions is inhibition of bacterial nucleic acid synthesis.
128FF3.jpg|Fig. 128.3 Mechanism of action of antifungal drugs. The different classes of antifungal drugs exert their effects at different sit
es in the fungal cell. Notably, ciclopirox olamine and polyenes have more than o
ne site of action.
128FF4.jpg|Fig. 128.4 Ergosterol synthesis pathway. Squalene
is coverted to lanosterol by squalene epoxidase. This enzyme is inhibited by the

allylamine and benzylamine antifungals. 14-α demethylase converts lanoster
ol to ergosterol. Imidazole and triazole antifungals inhibit this conversion.
128FF5.jpg|Fig. 128.5 Mechanism of action of acyclovir. Acycl
ovir, a purine analogue, has a high affinity for HSV-1, HSV-2, and VZV thymidine
kinase, which phosphorylates and activates the drug. Human cellular guanylate k
inase then phosphorylates acyclovir twice to transform it into acyclovir triphos
phate, which blocks viral DNA synthesis by competitively inhibiting and inactiva
ting viral DNA polymerase and by becoming irreversibly incorporated into the vir
al DNA chain, causing DNA chain termination. Valacyclovir, penciclovir and famci
clovir have mechanisms of action similar to acyclovir.
128FT1.jpg|Table 128.1 Bacteriostatic versus bactericidal drugs. Clindamycin may be either bacteriostatic or bactericidal depending on the su
sceptibility of the infecting organism and the concentration achieved at the sit
e of infection.
128FT2.jpg|Table 128.2 Topical antibacterials used for acne vulga
ris and rosacea.
128FT3.jpg|Table 128.3 Mechanisms of action of topical antibacter
ial agents used to treat acne vulgaris and rosacea.
128FT4.jpg|Table 128.4 Side effects of topical antibacterial agen
ts used for acne vulgaris and rosacea.
128FT5.jpg|Table 128.5 Topical antibacterial agents used for supe
rficial infections.
128FT6.jpg|Table 128.6 Mechanisms of action of topical antibacter
ial agents used for superficial infections.
128FT7.jpg|Table 128.7 Sites of action of different classes of sy
stemic antibacterial drugs.
128FT8.jpg|Table 128.8 Penicillins.
128FT9.jpg|Table 128.9 Dosages of commonly used penicillins.
128FT10.jpg|Table 128.10 Different classes of cephalosporins and
routes of administration.
128FT11.jpg|Table 128.11 Dosages of commonly prescribed cephalosp
orins.
128FT12.jpg|Table 128.12 Systemic macrolides.
128FT13.jpg|Table 128.13 Dosages of commonly used macrolides.
128FT14.jpg|Table 128.14 Dosages and routes of administration of
the tetracyclines.
128FT15.jpg|Table 128.15 Quinolones. *Withdrawn from US marke
t.
128FT16.jpg|Table 128.16 Topical antifungal agents. Other top
ical agents with antifungal activity not listed in this table include Whitfield&
#8217;s ointment (benzoic acid and salicylic acid), selenium sulfide, sodium thi
osulfate, salicylic acid and sulfur, zinc pyrithione, iodoquinol, haloprogin, ma
fenide, amorolfine, propylene glycol and benzoyl peroxide.
128FT17.jpg|Table 128.17 Systemic antifungal agents. Although
it is not included in the table, potassium iodide has antifungal activity and i
s used in cutaneous sporotrichosis.
128FT18.jpg|Table 128.18 Sites of action of antifungal drugs.
128FT19.jpg|Table 128.19 Indications for systemic antifungal agen
ts. *Resistant superficial fungal infections treated by systemic terbinafine
and azole antifungals include tinea corporis, tinea cruris and tinea pedis. The
azoles are also used for pityriasis versicolor. Certain of these indications ma
y not be available in some countries.
128FT20.jpg|Table 128.20 Dosages of terbinafine.
128FT21.jpg|Table 128.21 Adult dosing of oral itraconazole.
128FT22.jpg|Table 128.22 Dosing of fluconazole. *If the patie
nt is less than 14 days old, dosing is every 24–72 hours. If the patient i
s over 14 days old, dosing is every 24 hours.
128FT23.jpg|Table 128.23 Oral dosing of griseofulvin. To incr
ease absorption, griseofulvin microsize should be taken with a fatty meal.
128FT24.jpg|Table 128.24 Dosing of amphotericin B.

128FT25.jpg|Table 128.25 Side effects of systemic azole antifunga
l agents.
128FT26.jpg|Table 128.26 Drug interactions of systemic azole anti
fungal agents. K, ketoconazole; I, itraconazole; F, fluconazole; V, voricona
zole.
128FT27.jpg|Table 128.27 Topical antiherpetic antiviral agents.
128FT28.jpg|Table 128.28 Comparative susceptibility of herpesviru
ses to antiviral drugs.
128FT29.jpg|Table 128.29 Indications and dosages of systemic anti
herpetic drugs. Dosage frequency and amount must be adjusted for renal failu
re and dialysis. *Or until healed.
128FT30.jpg|Table 128.30 Side effects of systemic antiviral agent
s.
129FF1.jpg|Fig. 129.1 Ulceration site of interferon-β inject
ion in a woman with multiple sclerosis. There is hyperpigmentation at previo
us injection sites.
129FF2.jpg|Fig. 129.2 Imiquimod effects on Th1 and Th2 balance.
129FF3.jpg|Fig. 129.3 The effects of GM-CSF and G-CSF.
129FF4.jpg|Fig. 129.4 Urticarial plaque at the site of GM-CSF inj
ection.
129FF5.jpg|Fig. 129.5 Mechanism of action of tacrolimus and pimec
rolimus. FKBP, FK506-binding protein.
129FF6.jpg|Fig. 129.6 Sites of action of bioengineered immunomodu
lators. A Activation of T cells requires two signals. The first occurs when
the major histocompatibility complex antigen interacts with the T cell receptor.
A second costimulatory signal is required for T cell activation to occur. B Sites of action of Alefacept. C Sites of action of Efalizumab. D Sites of action of anti-CD80 antibody and CTLA-4I g.
129FF7.jpg|Fig. 129.7 Infliximab and etanercept: mechanisms of ac
tion.
129FT1.jpg|Table 129.1 The interferons. These agents are FDA
approved (see Table 129.4). §Used for the treatment of multiple
sclerosis.
129FT2.jpg|Table 129.2 Interferons: half-life and peak effect3.
129FT3.jpg|Table 129.3 Mechanisms of action for interferons.
129FT4.jpg|Table 129.4 Clinical diseases treated with interferons
. *FDA approved. †Life-threatening, severe, corticosteroid-resistant.
§Less effective than IFN-α.
129FT5.jpg|Table 129.5 Frequency of adverse events associated wit
h interferon therapy (n = 143)*101. *Dose not specified. &
#8224;Agranulocytosis or pancytopenia very uncommon – primarily in setting
of hepatitis C viral infection or when combined with cytotoxic drugs. ‡Ma
gnitude of LFT changes not specified.
129FT6.jpg|Table 129.6 Therapy of superficial BCC with 5% imiquim
od cream.
129FT7.jpg|Table 129.7 Therapy of nodular BCC with 5% imiquimod c
ream.
129FT8.jpg|Table 129.8 Recombinant forms of commercially availabl
e GM-CSF and G-CSF.
130FF1.jpg|Fig. 130.1 Reactions to topical 5-fluorouracil. No
te the erythema, periorbital edema and crusting in the areas of solar damage. B Courtesy of Ron Rapini, M.D.
130FF2.jpg|Fig. 130.2 Calcitriol, the active form of vitamin D<su
b>3.
130FF3.jpg|Fig. 130.3 Calcipotriol, a 1,25(OH)2D3
 analogue.
130FT1.jpg|Table 130.1 Cutaneous absorption by anatomic site.

*Taken as reference. From Feldman RJ, Maibach HI. Regional variation in percuta
neous penetration of 14C cortisol in man. J Invest Dermatol. 1967;48:181–3
.
130FT2.jpg|Table 130.2 Classification of external preparations.
130FT3.jpg|Table 130.3 Potential systemic side effects of topical
medications. *This side effect is not definitely established.
130FT4.jpg|Table 130.4 Topical drugs with minimal risk during pre
gnancy and lactation8. FDA pregnancy categories: A, contro
lled studies in humans show no risk in any trimester of pregnancy; B, no
evidence of risk in humans and chance of fetal harm is remote (either controlled
studies in pregnant women have shown no risk despite adverse findings in animal
s, or human studies have not been done but animal studies have shown no fetal ri
sk); C, risk cannot be ruled out and there is a chance of fetal harm, alt
hough the benefits may outweigh the risks (well-controlled human studies are lac
king and animal studies have shown risk to fetus or are also lacking). *Contrain
dicated during the first trimester. †Over-the-counter topical t
reatments. ‡Topical administration of intravaginal yeast medica
tions is not advised close to term because there is a risk of contamination if m
embranes have ruptured.
130FT5.jpg|Table 130.5 Commonly used topical agents for erosions,
ulcers and burns. *Its hypotonicity makes it unsuitable for large burned ar
eas.
130FT6.jpg|Table 130.6 Application of EMLA to intact skin –
recommended maximum pediatric dose, area and time. These are broad guidelin
es for avoiding systemic toxicity in patients with normal intact skin and normal
hepatic and renal function.
130FT7.jpg|Table 130.7 Generic and trade names of active vitamin
D3 analogues.
130FT8.jpg|Table 130.8 Treatment of psoriasis – comparative
studies with calcipotriol.
130FT9.jpg|Table 130.9 Combination studies with calcipotriol.
131FF1.jpg|Fig. 131.1 Dark blue discoloration of the shins due to
chloroquine.
131FF2.jpg|Fig. 131.2 Azathioprine hypersensitivity reaction.
Pink to red macules, papules and areas of confluence are seen. Courtesy of Kalm
an Watsky, M.D.
131FF3.jpg|Fig. 131.3 Post-inflammatory hyperpigmentation seconda
ry to gold eruption. There were features of both a lichenoid drug eruption a
nd a pityriasis rosea-like drug eruption.
131FF4.jpg|Fig. 131.4 Effect of thalidomide on subacute cutaneous
lupus erythematosus. The patient's disease was not controlled despite predn
isone (60 mg/day), hydroxychloroquine (600 mg/day) and isotretinoin (6
0 mg/day), all for at least two months (A). Thalidomide (50–10
0 mg/day) was begun and the lesions resolved over 6 to 8 weeks. Courtesy of
Jean Bolognia, M.D.
131FT1.jpg|Table 131.1 Method of action.
131FT2.jpg|Table 131.2 Side effects of systemic drugs used in der
matology. *Only used as intralesional injection. †Not permanent if gui
delines are followed.
131FT3.jpg|Table 131.3 Classification of histologic findings in l
iver biopsies. Data from Roenigk H, Auerbach R, Maibach HI, et al. Methotrex
ate in psoriasis: Revised guidelines. J Am Acad Dermatol. 1988;19:145–56.
132FF1.jpg|Fig. 132.1 Mycophenolate metabolism. Mycophenolate
is hydrolyzed to mycophenolic acid (MPA). Following enterohepatic recirculation
, MPAG is excreted into the gut via bile acid secretion. In the gut, bacteria re
move the glucuronide chain to produce MPA, the active molecule, which is then re
absorbed through the gut wall. Cyclosporin and tacrolimus block UDPGT (UDP-glucu
ronyl transferase) and thereby increase MPA.
132FF2.jpg|Fig. 132.2 P-Glycoprotein. This is an ATP-dependen

t plasma membrane glycoprotein that functions as a drug transporter and hence af
fects both drug absorption and elimination. Adapted from Kartner N, Ling V. Scie
ntific American 1989;260:44–51.
132FF3.jpg|Fig. 132.3 The cytochrome P-450 enzymes.
132FF4.jpg|Fig. 132.4 CYP3A4 inhibition by grapefruit juice and e
nhanced cyclosporine absorption.
132FT1.jpg|Table 132.1 Patient risk factors for drug interactions
13.
132FT2.jpg|Table 132.2 P-Glycoprotein substrates.
132FT3.jpg|Table 132.3 Inhibitors of P-glycoprotein.
132FT4.jpg|Table 132.4 Drug interactions that increase risk of su
bstrate drug toxicity2,3. *No longer commercially available in th
e US except special requests. **Also A5 and A7. ***Not available in US or UK. **
**Not available in US.
132FT5.jpg|Table 132.5 Influences on cytochrome P450 activity.
132FT6.jpg|Table 132.6 Drug interactions that reduce the efficacy
of substrates.
132FT7.jpg|Table 132.7 Substrates of CYP3A4,5,745.
132FT8.jpg|Table 132.8 CYP3A4 inhibitors and inducers45. Drugs in italics are particularly potent inhibitors.
132FT9.jpg|Table 132.9 Drug metabolizing enzymes CYP1A2, 2C9 and
2C19: selected substrate inhibitors and inducers44,45.
132FT10.jpg|Table 132.10 Substrates and inhibitors of CYP2D6
44,45.*Applies to metabolite rather than the parent drug. Drugs in ita
lics are particularly potent inhibitors.
132FT11.jpg|Table 132.11 Drugs and foods with differing potential
for drug–drug interactons based on metabolism. *Withdrawn from the ma
rket in the US and UK. **Withdrawn from the market in the US. ***Available in U
133FF1.jpg|Fig. 133.1 Basic aspects of medicine. A The three
mechanisms of treatment. B A dedicated physician can cause remarkable effects ev
en without an objective contribution.
133FF2.jpg|Fig. 133.2 Contact allergy to propolis. This is a
frequently used topical agent in central Europe.
133FF3.jpg|Fig. 133.3 Phototoxic reaction due to herbal tea.
133FF4.jpg|Fig. 133.4 Pseudolymphoma at the sites of Hirudo medic
inalis (medicinal leech) application.
133FT1.jpg|Table 133.1 Commonly used alternative medical treatmen
ts. According to Ernst, 20001, modified according to Federspiel & Herbst
, 19922.
133FT2.jpg|Table 133.2 Dietary supplements and effects on coagula
tion. Reproduced with permission from Collins & Dufresne, 200219</s
up>.
134FF1.jpg|Fig. 134.1 Electromagnetic spectrum with expanded UV r
egion.
134FF2.jpg|Fig. 134.2 Phototherapy action spectrum of psoriasis. The phototherapy action spectrum of psoriasis is plotted as the reciprocal o
f the lowest effective daily dose to clearing vs. wavelength. Red dashed line sh
ows human erythema action spectrum. Blue line is the action spectrum of psoriasi
s. Circles represent the reciprocal of the lowest daily dose to clear psoriasis
(295, 300, 304, 313 nm). Presently, only narrowband UVB sources are availab
le, which emit between 311 and 313 nm. Adapted from Parrish and Jaenicke .
134FF3.jpg|Fig. 134.3 Emission spectra of broadband and narrowban
d UVB bulbs used for phototherapy. Philips TL12, broadband UVB bulb; Philips
TL01, narrowband UVB bulb.
134FF4.jpg|Fig. 134.4 Treatment schedule for broadband and narrow
band UVB therapy.
134FF5.jpg|Fig. 134.5 Narrowband phototherapy for vitiligo. A
Before treatment; B after 10 months of treatment (twice weekly).
134FF6.jpg|Fig. 134.6 Emission spectrum of a typical UVA-1 light

source (filtered metal halide lamp).
134FF7.jpg|Fig. 134.7 UVA-1 phototherapy of atopic dermatitis. High-dose (130 J/cm2, left side) versus medium dose (65 J
/cm2, right side) UVA-1 phototherapy of atopic dermatitis. A B
efore treatment; B after treatment (15 exposures). Note that there is no
difference in the therapeutic result. From Tzaneva et al.
134FF8.jpg|Fig. 134.8 Molecular structure of commonly used psoral
ens.
134FF9.jpg|Fig. 134.9 Monofunctional adducts and bifunctional add
ucts (crosslinks) between psoralen and pyrimidine base of DNA.
134FF10.jpg|Fig. 134.10 Typical spectrum of a UVA bulb (Philips T
L09) used for PUVA therapy.
134FF11.jpg|Fig. 134.11 Treatment schedule for oral and bath PUVA
.
134FF12.jpg|Fig. 134.12 PUVA treatment for psoriasis (5-MOP; four
times weekly). A Before treatment; B after 6 weeks of treatment.
134FF13.jpg|Fig. 134.13 PUVA treatment for CTCL (mycosis fungoide
s) (8-MOP; 4 times weekly). A Before treatment; B after 12 weeks of t
reatment.
134FT1.jpg|Table 134.1 Exposure doses for MED assessment with bro
adband and narrowband UVB sources (mJ/cm2). Physical doses as mea
sured with an integrated UV meter (Waldmann, Schwenningen, Germany).
134FT2.jpg|Table 134.2 PUVA-responsive diseases. †
Experience is limited to a small number of patients. *May flare.
134FT3.jpg|Table 134.3 Skin phototypes. aTypes I&#
8211;IV are determined by history; types V and VI by physical examination (racia
l descent). bPatients with erythrodermic psoriasis are to be classifi
ed as skin phototype I for determination of UVA dosage. cPatients wit
h this phototypes should be classified into a lower skin phototype category if t
he sunburning history so indicates.
134FT4.jpg|Table 134.4 Differences between the US and European pr
otocols.
135FF1.jpg|Fig. 135.1 Acute photosensitivity due to hematoporphyr
in. Meyer-Betz, who noted pain and swelling of exposed skin within minutes o
f injection of 200 mg of hematoporphyrin. Generalized photosensitivity last
ed more than 2 months. (Photograph taken from Dtsch Arch Klin Med. 1913;112:476.
)
135FF2.jpg|Fig. 135.2 Photosensitizer delivery and photodynamic e
ffects on target cells and tissue vasculature. Topical photosensitizers ALA
and methyl ALA diffuse through the stratum corneum into target epithelial cells.
Systemic photosensitizers arrive through the serum (ALA) or bound to LDL (e.g.
BPD). Oxygen is delivered via erythrocyte circulation. Systemically delivered ph
otosensitizers concentrate in endothelial cells and diffuse through the intersti
tium to target cells. ALA derived from any source is converted to PpIX within mi
tochondria. PpIX then leaks from the mitochondria to other cellular structures,
and eventually to the vasculature for removal. After sufficient time for photose
nsitizer partitioning to subcellular structures, target tissue is irradiated wit
h photoactivating light. During acute photodynamic injury, mitochondria leak cyt
ochrome c, initiating endonuclease activity, and plasma and nuclear membranes lo
se integrity. Acute injury in endothelial cells leads to thrombus formation and
vascular collapse. Target cell and tissue oxygen delivery cease. Both apoptosis
and ischemic necrosis contribute to irreversible target cell injury and death.
135FF3.jpg|Fig. 135.3 Photochemical activation of the photodynami
c process: the Jablonski energy state diagram. See text for explanation.
135FF4.jpg|Fig. 135.4 Absorption spectrum of protoporphyrin IX. The absorption spectrum demonstrates the probability of absorption for each w
avelength of light. It reveals the major absorption (photoactivation) peaks of t
he PpIX. The blue (417 nm) and red (630 nm) wavelengths typically used
to activate PpIX in photodynamic therapy are designated (spectrum for PpIX diss
olved in pyridine).
135FF5.jpg|Fig. 135.5 Chemical structures of photosensitizers and
pro-photosensitizers. ALA (A), mALA (B), PpIX (C), porfimer sodium (D), ver
teporfin (E), temoporfin (F), SnET2 (G).
135FF6.jpg|Fig. 135.6 Photodynamic therapy of nodular basal cell
carcinoma (BCC) using IV BPD and red light. A Nodular BCC prior to tr
eatment. B At 48 hours early tissue necrosis correlates with pretreatment
tumor, with a lesser response in normal surrounding skin. C At 9 days ti
ssue necrosis affects the tumor and some adjacent irradiated skin. Necrotic tiss
ue went on to slough and the resulting superficial ulcer healed. D At 3 m
onths the treatment site shows an erythematous scar. E At 2 years the tre
atment site has been replaced with a pale soft scar with no evidence of recurren
t tumor.
135FF7.jpg|Fig. 135.7 Topical ALA photosensitization of nodular b
asal cell carcinoma. A White light image of a nodular BCC after topic
al ALA application. B The same tumor viewed under blue excitation light,
revealing pink PpIX fluorescence in the BCC and lighter signal in adjacent photo
damaged skin. C The same tumor viewed using blue excitation light and a r
ed (635 +/− 10 nm) filter to reveal only PpIX fluorescence, now seen
in the tumor, nearby actinic keratoses, and normal hair follicles.
135FF8.jpg|Fig. 135.8 Oral ALA photosensitization of BCC. 
A Routine light microscopy of a stained frozen section demonstrates a morphe
aform pattern BCC (hematoxylin & eosin, 200×). B The same frozen
section examined by fluorescence microscopy shows PpIX fluorescence in every tu
mor island several hours after 40 mg/kg oral ALA (200×).
135FF9.jpg|Fig. 135.9 Photodynamic therapy of superficial BCC usi
ng oral ALA and red light. A A superficial BCC prior to treatment. B Immediately after light exposure the treatment area manifests erythema an
d edema. C At 3 days erythema, edema, and light scale are present. D At 3 months complete healing has occurred without evidence of scarring. Histo
pathologic examination of this treatment site showed no tumor present. In B, C &
#38; D, the tumor site is marked by four small India ink tattoos.
135FF10.jpg|Fig. 135.10 Photosensitivity after oral ALA. Twen
ty-four hour appearance of a patient who sustained a phototoxic reaction by walk
ing in bright sunlight several hours after oral ALA administration. The reaction
resolved with desquamative peeling, concluding several days later.
135FT1.jpg|Table 135.1 Photosensitizers for dermatologic PDT.
136FF1.jpg|Fig. 136.1 Divergence and effects of convergence.
136FF2.jpg|Fig. 136.2 Laser system.
136FF3.jpg|Fig. 136.3 Spatial coherence. A Portable flashligh
t. B Laser.
136FF4.jpg|Fig. 136.4 Laser light absorbtion and scattering by th
e skin.
136FF5.jpg|Fig. 136.5 Absorption spectra. The heterogeneous a
bsorption spectra of chromophores allows selective photothermolysis to work.
136FF6.jpg|Fig. 136.6 The electromagnetic spectrum. The visib
le portion is only a small range of the spectrum.
136FF7.jpg|Fig. 136.7 The effects of spot size on scattering: sam
e subsurface fluence. The larger spot size allows more photons to remain wit
hin a beam's diameter, whereas with a smaller spot size a greater fraction of ph
otons scatter outside the beam and are ineffective. Thus subsurface fluence appe
ars at deeper levels with a larger spot.
136FF8.jpg|Fig. 136.8 Depth of penetration by various lasers.
136FT1.jpg|Table 136.1 Pulsewidths and targets of selective photo
thermolysis.
136FT2.jpg|Table 136.2 Laser and laser dermatology terms.
136FT3.jpg|Table 136.3 Lasers in medicine.
137FF1.jpg|Fig. 137.1 Port-wine stain. A Before treatment. B Purpuric response immediately after treatment with the 585 nm, 450&n
bsp;ms PDL. C Six weeks after the fourth PDL treatment.
137FF2.jpg|Fig. 137.2 Superficial hemangioma. A Before treatm

ent. B After a series of PDL treatments. Courtesy of Jerome Garden, M.D.
137FF3.jpg|Fig. 137.3 Recalcitrant plantar wart. A Before tre
atment. B After a single PDL treatment. Courtesy of Ian Webster, M.D.
137FF4.jpg|Fig. 137.4 Solar lentigines. A Before and B
six weeks after a single Q-switched ruby laser treatment there is lightening of
the treated lesions. A further treatment is required to achieve full imp
rovement
137FF5.jpg|Fig. 137.5 Café-au-lait macule. A Before and
B complete clearing after a series of Q-switched ruby laser treatments. C
ourtesy of Tadashi Tezuka, M.D.
137FF6.jpg|Fig. 137.6 Amateur tattoo on the back. A Before tr
eatment. B Total clearing after five Q-switched Nd:YAG laser treatments.
137FF7.jpg|Fig. 137.7 Severe photodamage. A Before treatment.
B One year after CO2 laser skin resurfacing.
137FF8.jpg|Fig. 137.8 Excessive chin hair. A Before and B after four long-pulse ruby laser treatments there is almost complete and per
manent hair growth reduction.
137FT1.jpg|Table 137.1 Pulsed lasers and light sources for vascul
ar lesions.
137FT2.jpg|Table 137.2 Laser for pigmented lesions.
137FT3.jpg|Table 137.3 Selection of Q-switched lasers for differe
nt colors of tattoo ink.
137FT4.jpg|Table 137.4 Representative high peak power CO2</s
ub> and Er:YAG lasers.
137FT5.jpg|Table 137.5 Indications for resurfacing with CO2 and Er:YAG lasers.
137FT6.jpg|Table 137.6 Side effects and complications of laser sk
in resurfacing.
137FT7.jpg|Table 137.7 Cooling systems for lasers.
137FT8.jpg|Table 137.8 Lasers for hair removal.
137FT9.jpg|Table 137.9 Laser or light source selection for hair r
emoval.
138FF1.jpg|Fig. 138.1 Key observations during cryosurgery.
138FF2.jpg|Fig. 138.2 Cryosurgical methods. A The cotton-tipp
ed applicator method used in the treatment of veruccae vulgaris, including periu
ngual warts. B Superficial freezing used for treating benign lesions and
actinic keratoses. C Cryoprobe method which is useful for round lesions a
nd those on flat surfaces. D Surface extension of the ice ball: note the
diminution of the temperature as the ice ball progresses outwards; this can be d
etermined with palpation. E Aggressive freezing is deeper and employs the
rmocouple monitoring of tissue temperature.
138FF3.jpg|Fig. 138.3 A squamous cell carcinoma on the cheek in a
95-year-old woman. A The lesion measures 4.5 cm × 3 cm. B
 Cryosurgery to upper half of the lesion. Segmental treatment was used to re
duce the morbidity. Note lateral spread of freeze and protection of ear canal wi
th cotton. C Tissue response after cryosurgery: exudation and sloughing o
ne week after treatment. D The completely healed site shows an excellent
cosmetic result four months after second section of tumor was treated.
138FF4.jpg|Fig. 138.4 Basal cell carcinoma on right lower eyelid.
A Papular lesion at margin of lid in an 82-year-old woman. B Cryosur
gery to lesion: note placement of thermocouple needle and protection of eye. 
C The healed cryosurgical site six months after treatment. Excellent cosmeti
c result; note loss of cilia.
138FT1.jpg|Table 138.1 Advantages in the use of cryosurgery.
138FT2.jpg|Table 138.2 Benign conditions amenable to cryosurgery.

139FF1.jpg|Fig. 139.1 Electron beam depth–dose curve.
139FF2.jpg|Fig. 139.2 Depth dose of electron beam. A Dose of
6 MeV and 12 MeV beams. B Demonstration of the bolus effect, of
fering more appropriate dose of radiation to the skin surface.

139FF3.jpg|Fig. 139.3 Psoriasis of the nails. A 46-year-old f
emale patient, A before and B 8 months after Grenz-ray treatment,
five doses of 2 Gy (10 Gy total), given twice weekly.
139FF4.jpg|Fig. 139.4 Hand eczema. Chronic recalcitrant hand
eczema in a 54-year-old cement worker, A before and B 4 months aft
er Grenz-ray treatment, six doses of 1 Gy (6 Gy total) given twice wee
kly.
139FF5.jpg|Fig. 139.5 Hailey–Hailey disease. A 64-yearold patient, A before and B 3 months after Grenz-ray treatment, si
x doses of 1 Gy (6 Gy total) given twice weekly.
139FF6.jpg|Fig. 139.6 Indications for radiation. Indications/
radiosensitivity of different skin tumors.
139FF7.jpg|Fig. 139.7 Actinic keratoses. Disseminated actinic
keratoses in a 71-year-old woman, A before and B 6 months after G
renz-ray treatment, six times 6 Gy (36 Gy), twice weekly.
139FF8.jpg|Fig. 139.8 Lentigo maligna. LM in a 59-year-old pa
tient on the right cheek, A before and B 6 months after Grenz-ray
treatment, 10 times 10 Gy (100 Gy), twice weeky.
139FF9.jpg|Fig. 139.9 Basal cell carcinoma. BCC in a 70-yearold woman on the right ear, A before and B 8 months after soft X-r
ay treatment (30 kV), 12 times 4 Gy (48 Gy), twice weekly.
139FF10.jpg|Fig. 139.10 Squamous cell carcinoma. SCC in 79-ye
ar-old man on the scalp, A before and B one year after soft X-ray
treatment (50 kV), 28 times 2 Gy (56 Gy), daily.
139FF11.jpg|Fig. 139.11 Lentigo maligna melanoma. LMM in a 60
-year-old woman on the right cheek, A before and B 2 years after s
oft X-ray treatment (40 kV), seven times 6 Gy (42 Gy), three time
s a week.
139FF12.jpg|Fig. 139.12 Mycosis fungoides. Mycosis fungoides
in an 80-year-old man A before and B 1 month after soft X-ray trea
tment (50 kV), six times 2 Gy (12 Gy), three times a week.
139FF13.jpg|Fig. 139.13 Kaposi's sarcoma. KS (AIDS-associated
) in a 45-year-old man, on the left foot, A before and B 2 months
after soft X-ray treatment (40 kV), four times 4 Gy (16 Gy), thre
e times a week.
139FT1.jpg|Table 139.1 Recommended doses: benign skin diseases.
139FT2.jpg|Table 139.2 Recommended doses: malignant tumors.
139FT3.jpg|Table 139.3 Side effects of total body electron beam t
herapy.
140FF1.jpg|Fig. 140.1 Applications of different waveforms in elec
trosurgery.
140FF2.jpg|Fig. 140.2 Seborrheic keratosis on the upper lip. A Given its epidermal location, electrosurgical destruction should employ a curr
ent that provides the most superficial type of tissue damage. B Under loc
al anesthesia, the lesion is treated by electrodesiccation. Delivery of current
is stopped when the lesion begins to ‘bubble’. C In lieu of a
curette, a gauze pad is useful for removing charred tissue after desiccation of
superficial lesions. D There is minimal bleeding, indicating that damage
did not penetrate deeply into the dermis.
140FF3.jpg|Fig. 140.3 Telangiectasias on nose and upper lip being
treated by fine needle electrocoagulation. A Pre-operative photograph shows
linear telangiectasias on the nose and upper lip. B The electrode consis
ts of a hub adapter with a 30-gauge metal-hubbed needle attached. The machine is
energized at a low power setting and the electrode momentarily touches the skin
surface, along the length of the vessel being treated, at 3 to 4 mm interv
als. The patient experiences some discomfort during the procedure, but this is u
sually tolerable. C The same patient immediately after treatment. This te
chnique is usually performed quickly without anesthesia.
140FF4.jpg|Fig. 140.4 Bipolar forceps attached to an electrosurgi

cal apparatus. These are useful for providing pinpoint electrocoagulation in
hemostasis. Bipolar electrocoagulation is also recommended for use in patients
with cardiac pacemakers or ICDs.
140FF5.jpg|Fig. 140.5 Rhinophyma. A Moderately severe rhinoph
yma in a middle-aged man. B Immediately after electrosurgical planing of
excess sebaceous glands. Care is taken to perform subtotal removal as very aggre
ssive therapy can result in significant scarring and possible deformity caused b
y scar contracture. C Four weeks later, healing with good cosmetic outcom
e is noted. During healing, the wound is kept moist with an antibiotic ointment
and semi-occlusive dressings.
140FT1.jpg|Table 140.1 Common dermatologic indications for electr
osurgery.
141FF1.jpg|Fig. 141.1 The three overlapping phases of wound heali
ng.
141FF2.jpg|Fig. 141.2 Comparison of a partial thickness and a ful
l thickness wound. The partial thickness wound is one in which the epidermis
and part of the dermis are missing but the adnexal structures remain. A full th
ickness wound is one in which all of the epidermis and dermis adnexal structures
are missing.
141FF3.jpg|Fig. 141.3 Sacral pressure in a nursing home patient.
141FF4.jpg|Fig. 141.4 Partial thickness wound epithelialization. The red is the wound bed and the white within the wound bed are the remainin
g adnexal structures. After partial thickness wounding (top panel), microscopic
adnexal structures remain as a source of keratinocytes. During the first few day
s after wounding, cells migrate from both the wound edges and the adnexal struct
ures (middle panel) and eventuate in epithelialization (bottom panel).
141FF5.jpg|Fig. 141.5 Full thickness wounds. A Full thickness
wound created in porcine wound healing model. B Full thickness wound cre
ated in center of tattoo grid, which has been allowed to granulate for several d
ays. C Same wound as B, after healing. Note contraction of the wou
nd that has occurred which results in distorted grid.
141FF6.jpg|Fig. 141.6 The inflammatory phase of wound healing. Cells are recruited to the wound site and initiate a healing cascade mediated
primarily by cytokines including platelet-derived and macrophage-derived factors
.
141FF7.jpg|Fig. 141.7 The proliferative phase of wound healing. Deposition of matrix materials allow cells to proliferate leading to the deve
lopment of granulation tissue and re-epithelialization.
141FF8.jpg|Fig. 141.8 Cellular activity in the proliferative phas
e.
141FF9.jpg|Fig. 141.9 Granulation tissue characterizes the prolif
erative phase with angiogenesis and fibroplasia.
141FF10.jpg|Fig. 141.10 Possible methods of keratinocyte migratio
n.
141FF11.jpg|Fig. 141.11 The remodeling phase of wound healing.
141FF12.jpg|Fig. 141.12 Normal type I collagen (×10 0
00).
141FF13.jpg|Fig. 141.13 Occlusive dressings. Use of occlusive
dressings on acute wounds speeds healing and improves cosmesis even with primar
ily closed wounds. A Hydrocolloid dressing covering a biopsy site on the
right cheek. B Polyurethane film dressing covering a sutured wound.
141FF14.jpg|Fig. 141.14 Split thickness skin graft donor site reg
rafted to speed healing. A Donor site regrafted with meshed and pinch autogr
afts to speed healing. B Comparison of donor sites treated with meshed bi
layered allogeneic living skin equivalent (top left), meshed autograft (top righ
t), and polyurethane film dressing (bottom left). The meshed bilayered allogenei
c living skin equivalent and the meshed autograft both speed healing compared to
the film dressing.

141FT1.jpg|Table 141.1 Different types of metalloproteinases (MMP
s).
141FT2.jpg|Table 141.2 Growth factors found to speed healing of a
cute wounds in humans.
142FF1.jpg|Fig. 142.1 Bony landmarks of the skull. A Anterior
view. B Lateral view.
142FF2.jpg|Fig. 142.2 Topographic anatomy and important cutaneous
landmarks.
142FF3.jpg|Fig. 142.3 Veins of the face.
142FF4.jpg|Fig. 142.4 Anatomy of the neck.
142FF5.jpg|Fig. 142.5 Cross-sectional anatomy of fascial planes o
f the upper face.
142FF6.jpg|Fig. 142.6 Skin tension lines overlying facial muscles
. Note that wrinkles are often directed perpendicularly to the underlying mu
scle fibers of facial expression.
142FF7.jpg|Fig. 142.7 Muscles of facial expression. A Anterio
r view. B Lateral view.
142FF8.jpg|Fig. 142.8 Reservoirs of redundant skin.
142FF9.jpg|Fig. 142.9 Arterial supply of the face.
142FF10.jpg|Fig. 142.10 The facial (motor) nerve.
142FF11.jpg|Fig. 142.11 Trigeminal cutaneous sensory nerves (cran
ial nerve V).
142FF12.jpg|Fig. 142.12 Deep to superficial pathways of sensory n
erve branches.
142FF13.jpg|Fig. 142.13 Lymphatic drainage of head and neck.
142FT1.jpg|Table 142.1 Innervation of the muscles of facial expre
ssion via cranial nerve VII (the facial nerve)4,14.
143FF1.jpg|Fig. 143.1 Chemical structure of the ester and amide g
roup local anesthetics. The aromatic (hydrophobic) end is joined to the amin
e (hydrophilic) end with an ester or amide linkage.
143FF2.jpg|Fig. 143.2 Sensory innervation of the central face.
143FF3.jpg|Fig. 143.3 Skull exit points of central face sensory n
erves.
143FF4.jpg|Fig. 143.4 Locations of needle insertions for central
face nerve blocks.
143FF5.jpg|Fig. 143.5 Intraoral route for infraorbital nerve bloc
k. The needle is inserted cephalad between the premolar (bicuspid) teeth in
the mid-pupillary line.
143FF6.jpg|Fig. 143.6 Intraoral route for mental nerve block.
The needle is inserted caudally between the premolar (bicuspid) teeth in the mi
d-pupillary line.
143FF7.jpg|Fig. 143.7 Sensory innervation of the palmar surface a
nd dorsal surface of the right hand.
143FF8.jpg|Fig. 143.8 Cutaneous markers for the median nerve loca
tion at the wrist. Note thumb and little finger apposition and wrist flexion
to visualize the palmaris longus tendon. (X, needle entry point; PL, palmaris l
ongus tendon.)
143FF9.jpg|Fig. 143.9 Sensory innervation of the dorsal surface a
nd plantar surface of the right foot.
143FF10.jpg|Fig. 143.10 Posterior tibial and sural nerve blocks.
143FF11.jpg|Fig. 143.11 Superficial peroneal, saphenous, and deep
peroneal nerve blocks. Note great toe dorsiflexion to visualize the extenso
r hallucis longus tendon.
143FT1.jpg|Table 143.1 Local anesthetics for infiltrative and ner
ve block anesthesia. In clinical practice, the duration of anesthesia appear
s to be less than stated, especially for head and neck areas. Addition of epinep
hrine prolongs anesthesia by a factor of two
143FT2.jpg|Table 143.2 Differential diagnosis of local anesthetic

systemic reactions. In case of systemic reactions during or after local ane
sthetic injections, hemodynamic signs are helpful in determining the cause of th
e reaction
143FT3.jpg|Table 143.3 Topical anesthetics for mucous membrane an
d intact skin anesthesia. Anesthetics for topical skin anesthesia require ap
plication 0.5–2 hours prior to surgery under occlusion for maximal effect
Generic name Trade name Concentration (%) Type Primary use
143FT4.jpg|Table 143.4 Tumescent anesthesia formula. For tume
scent anesthesia, a final concentration of 0.05 to 0.1% lidocaine with 1:1000 00
0 is prepared. Hyaluronidase may be added to enhance diffusion and corticosteroi
ds may be added to reduce inflammation, edema and possibly fibrosis
144FF1.jpg|Fig. 144.1 Needle nomenclature by two representative m
anufacturers.
144FF2.jpg|Fig. 144.2 Needle anatomy. The shank body and poin
t are shown, and specific needle points for different types of cutting.
144FF3.jpg|Fig. 144.3 Needle shapes. The most common shape us
ed in skin surgery is the 3/8 circle.
144FF4.jpg|Fig. 144.4 Mohs tray. Tray setup for basic Mohs mi
crographic surgery includes (from left to right) Bishop–Harmon forceps, No
. 7 handle with No. 15 blade, and Supercut® Gradle scissors. Instruments co
urtesy of George Tiemann & Company, Hauppauge, NY, USA.
144FF5.jpg|Fig. 144.5 Facial surgery tray or repair tray. Tra
y setup for facial surgery/repair includes (from left to right) Bishop–Har
mon forceps, delicate standard skin hook, No. 7 handle with No. 15 blade, delica
te Webster needle holder, Supercut® Gradle scissors, Supercut® curved
iris scissors, delicate Supercut® Shea undermining scissors, small hemostat
, towel clamp, and suture scissors. Instruments courtesy of George Tiemann &
Company, Hauppauge, NY, USA.
144FF6.jpg|Fig. 144.6 Trunk or extremity surgery tray. Tray s
etup for truncal or extremity includes (from left to right) Petrie dish, skin ho
ok, No. 7 handle with No. 10 blade, larger Halsey needle holder, Supercut®
curved iris scissors, Supercut® baby Metzenbaum undermining scissors, small
hemostat, towel clamp, Adson forceps, and suture scissors. Instruments courtesy
of George Tiemann & Company, Hauppauge, NY, USA.
144FF7.jpg|Fig. 144.7 Eyelid tray. Tray setup for eyelid surg
ery includes (from right to left) topical anesthetic, Teflon eyeshield, Beaver b
lade setup, Westcott (or Castroviejo) scissors, Bishop–Harmon forceps, and
ophthalmic ointment. Instruments courtesy of George Tiemann & Company, Haup
pauge, NY, USA.
144FF8.jpg|Fig. 144.8 Standard scalpel handles. From top to b
ottom: Beaver blade handle, No. 7 handle, and No. 3 handle. Instruments courtesy
of George Tiemann & Company, Hauppauge, NY, USA.
144FF9.jpg|Fig. 144.9 Blade remover. Instruments courtesy of
George Tiemann & Company, Hauppauge, NY, USA.
144FF10.jpg|Fig. 144.10 Standard delicate Webster and Halsey need
le holders. Instruments courtesy of George Tiemann & Company, Hauppauge,
NY, USA.
144FF11.jpg|Fig. 144.11 Standard scissors. From left to right
: Supercut® Gradle scissors, Supercut® iris scissors, and Supercut&#17
4; baby Metzenbaum scissors. Instruments courtesy of George Tiemann & Compan
y, Hauppauge, NY, USA.
144FF12.jpg|Fig. 144.12 Westcott scissors. Instruments courte
sy of George Tiemann & Company, Hauppauge, NY, USA.
144FF13.jpg|Fig. 144.13 Suture removal scissors with groove to gr
ab suture, and forceps. Instruments courtesy of George Tiemann & Company
, Hauppauge, NY, USA.
144FF14.jpg|Fig. 144.14 Hemostasis.
144FT1.jpg|Table 144.1 Commonly used absorbable sutures. Adap
ted from Wheeland et al., 199411 with permission from WB Saund
ers Company.
144FT2.jpg|Table 144.2 Commonly used non-absorbable sutures.
Adapted from Wheeland et al., 199411 with permission from WB S
aunders Company.
144FT3.jpg|Table 144.3 Commonly utilized sutures by site. Not
e that there is considerable variation depending upon the preference of the surg
eon (bias of authors and editors is admitted).
144FT4.jpg|Table 144.4 Antiseptic agents. Adapted from Leffel
l et al. 199737 with permission from John Wiley & Sons, In
c.
144FT5.jpg|Table 144.5 Sterilization methods.
145FF1.jpg|Fig. 145.1 Characteristics of the ideal wound dressing
.
145FF2.jpg|Fig. 145.2 Pressure dressing. A Antibiotic ointmen
t applied over sutures helps to prevent infection and prevents contact layer fro
m adhering directly to the wound. B Three layers of paper tape comprise t
he contact layer. C Rolled gauze or a cotton dental roll can be used to (
i) provide pressure for hemostasis; (ii) aid in conforming the dressing to the w
ound; and (iii) absorb excess exudate. The entire dressing is secured with addit
ional layers of tape.
145FF3.jpg|Fig. 145.3 Second intention healing. A Surgical wo
und immediately following Mohs micrographic surgery; semi-occlusive dressing wil
l be used. B Wound healing by second intention 3 weeks following surgery.
Note abundance of pink granulation tissue. C Fully re-epithelialized wou
nd 6 weeks following surgery.
145FF4.jpg|Fig. 145.4 Example of a polymer film used to occlude a
topical anesthetic cream.
145FF5.jpg|Fig. 145.5 Duoderm wound dressing in place over a natu
rally healing wound on the foot.
145FF6.jpg|Fig. 145.6 An example of a composite dressing.
145FF7.jpg|Fig. 145.7 Occlusive dressings for post-laser resurfac
ing. A In this side-by-side comparison, the patient's left face is dressed w
ith a foam dressing. B In this side-by-side comparison, the patient's rig
ht face is dressed using the open technique.
145FT1.jpg|Table 145.1 Occlusive dressings.
145FT2.jpg|Table 145.2 Which dressing for which wound? Reprod
uced with permission from Cohen IK, Diegelmann RF, Lindblad WJ. Wound Healing Bi
ochemical and Clinical Aspects. Philadelphia: WB Saunders; 1992. *Shading indica
tes that a particular dressing is recommended for the corresponding wound. 
†Ulcers on the lower extremities tend to exude more heavily than sim
ilar wounds in sacral or trochanter areas. ‡PT: Partial thickne
ss. ¶Tape is required to fix hydrogel dressings in place.
145FT3.jpg|Table 145.3 Dressing options for chronic cutaneous ulc
ers.
145FT4.jpg|Table 145.4 Tissue-engineered skin equivalents.
146FF1.jpg|Fig. 146.1 Local anesthesia injection. A Deep infi
ltration B Superficial infiltration.
146FF2.jpg|Fig. 146.2 Instrument tie. The suture is looped ar
ound the needle holder, then the needle holder grasps the short end and pulls it
through the loops to create a knot.
146FF3.jpg|Fig. 146.3 Common suturing techniques. A Interrupt
ed buried dermal stitch. The needle enters the deep surface of the wound, passes
through to the dermis, crosses the wound, enters into the dermis on the opposit
e side of the wound, and then exits the deep surface. The knot is in the deepest
portion of the wound. B Interrupted buried vertical mattress. Similar to
the interrupted buried dermal stitch, the needle passes more superficially in t
he dermis than when it crosses the wound. The knot is in the deepest portion of
the wound. C Simple interrupted epidermal stitch. The needle enters the e
pidermis, passes through superficial dermis, crosses the wound, enters into the
dermis on the opposite side of the wound, and then exits the epidermis. The knot
lies on the surface across the opposed wound edges. D Vertical mattress
stitch. The needle passes through the epidermis to the deep surface of the wound
, crosses the wound, enters the deep surface of the opposite side, and then pass
es through to the epidermis. It is then reversed and enters the epidermis on the
same side closer to the wound edge, passes through the dermis, crosses the woun
d, enters the opposite edge at the dermis, and passes up to the epidermis close
to the wound edge. The knot lies on the surface to one side of the wound edge. E Running epidermal stitch. The needle passes the suture in and out of a v
ertical path from epidermis to dermis, then dermis to epidermis from side to sid
e. There are two knots, one on each end. F Running subcuticular stitch. T
he needle passes the suture in and out of the upper dermis from side to side in
a horizontal plane. Two knots are visible, one on each end.
146FF4.jpg|Fig. 146.4 Curettage. The curette is held like a p
encil and drawn with pressure over the suspected basal cell carcinoma.
146FF5.jpg|Fig. 146.5 Snip (scissors) biopsy. A pedunculated
lesion is held with forceps and separated at the base with scissors.
146FF6.jpg|Fig. 146.6 Shave biopsy. A specimen is removed fro
m an elevated lesion by cutting with a blade held parallel to the skin surface.
146FF7.jpg|Fig. 146.7 Punch biopsy. A,B The skin punch is pus
hed into the lesion and rotated until the subcutaneous plane has been reached. C The base of the specimen is separated with scissors. D The defect
is often closed with a single interrupted stitch.
146FF8.jpg|Fig. 146.8 Incisional biopsy. Part of a tumor or d
eep process is removed by a wedge resection for diagnosis.
146FF9.jpg|Fig. 146.9 Fusiform excision. The ‘ellipse&#
8217; is actually a fusiform shape with the length: width ratio approximating 3:
1 and apical angles of 30–75 degrees.
146FF10.jpg|Fig. 146.10 Fusiform excision. The site is anesth
etized (A) and the margins are marked (B) The site is prepped with an antibacter
ial cleansing agent and draped with sterile cloths (C). Stabilizing the site wit
h traction, the epidermis of one side of the fusiform design is scored using a #
15 blade (D). The epidermis on the with sterile cloths (C). Stabilizing the site
with traction, the epidermis of one side of the fusiform design is scored using
a #15 blade (D). The epidermis on the opposite side of the lesion is then score
d (E).opposite side of the lesion is then scored (E). Incision is completed into
the appropriate plane in the subcutaneous tissue.opposite side of the lesion is
then scored (E). Incision is completed into the appropriate plane in the subcut
aneous tissue.opposite side of the lesion is then scored (E). Incision is comple
ted into the appropriate plane in the subcutaneous tissue. The specimen then sit
s up in the middleopposite side of the lesion is then scored (E). Incision is co
mpleted into the appropriate plane in the subcutaneous tissue. The specimen then
sits up in the middle of the wound like an island (F).
146FF11.jpg|Fig. 146.11 Undermining. Undermining facilitates
movement of skin into the defect, reduces wound closure tension, allows proper w
ound edge eversion and provides a wide area for distribution of redundant tissue
in the base of the wound.
146FF12.jpg|Fig. 146.12 Four cases of formation of dog-ears: geom
etric factors.
146FF13.jpg|Fig. 146.13 Repair of dog-ears by rule of halves.
146FF14.jpg|Fig. 146.14 Repair of dog-ears by straight excision. Dog-ears are protrusions that form on each end during closure of a disc-shap
ed defect (A). The first limb of the dog-ear repair is incised to the sub
cutaneous compartment by scissors or blade (B). The wound is undermined b
eneath the entire dog-ear in the same plane as the rest of the defect (C)
. The undermined dog-ear is draped over the incision. The arrow indicates the ap
ex which lies flat against the underlying skin surface. A scissors or blade is u
sed to complete the excision of the second limb of the dog-ear (D). The r
edundant tissue removed is a triangle, often called a Burow's triangle (E
). Subcutaneous stitches are placed to begin closure (F).
146FF15.jpg|Fig. 146.15 Repair of dog-ears by M-plasty. The l
imbs of the dog-ear are cut at a 30–45 degree angle from the end of the wo
und to about halfway toward the apex of the redundancy (A). After both li
mbs are cut and the wound is fully undermined beneath the dog-ear, the redundant
tissue can be draped over the incision. At this point, an M is visible (B). A Burow's triangle is removed from half the draped tissue (C). A seco
nd Burow's triangle is excised from the opposite side of the draped tissue (D
). A corner stitch is used to pull the point of the M-plasty into appropriat
e position. The needle enters the epidermis proximal to the expected position of
the point, passes into the dermis, crosses the wound and enters the dermis of t
he tip. It then passes horizontally through the dermis of the tip, crosses the w
ound again, enters the dermis opposite and passes to the epidermal surface (E
). The knot of the corner stitch lies across the wound proximal to the posit
ion of the point of the M-plasty (F).
146FF16.jpg|Fig. 146.16 Displacement of dog-ear.
146FT1.jpg|Table 146.1 Biopsy site selection.
146FT2.jpg|Table 146.2 Biopsy technique selection.
146FT3.jpg|Table 146.3 Preoperative history.
147FF1.jpg|Fig. 147.1 Scar contractions. Depiction of differe
nces in scar contraction between wounds that are undermined and those that are n
ot undermined prior to suture placement. A The contraction forces are sho
wn focused on the margins of the flap in a wound that was not widely undermined.
B Broad diffusion of contractile forces which are not concentrated at th
e flap margins making ‘pin-cushioning’ less likely in the widely und
ermined flap.
147FF2.jpg|Fig. 147.2 Scar contraction. A Sutured wound witho
ut wound edge eversion and without undermining of the surrounding tissue. B The results of scar contraction leading to inversion of the scars and ‘
pin-cushioning’ of the flap. C A wound sutured with eversion and wi
de undermining. D The canceling effect of scar contraction and wound ever
sion as well as the diffusion of scar contraction in the deep, undermined wound
plane.
147FF3.jpg|Fig. 147.3 Burow's triangle displacement flaps.
147FF4.jpg|Fig. 147.4 A Photograph of a wound extending into
the mid brow. B Closure with a single tangent advancement flap with the t
angent extending laterally and inferior to the brow and displacing a Burow's tri
angle to the more convenient lateral canthus. The lateral eyebrow is preserved,
advanced medially with the flap and realigned with the medial brow.
147FF5.jpg|Fig. 147.5 Classic Z-plasty. The tissue gain is de
picted after flap transposition in the direction of the middle arm of the Z-plas
ty.
147FF6.jpg|Fig. 147.6 Classic Zplasty. A Defect close to lid
margin. The wound is closed with a Z-plasty closure with the transposition of fl
aps at the upper medial and lower lateral aspects of the wound (B). This
is done to lengthen tissue in the direction of the palpebral margin to prevent e
ctropion as seen in fourth month post-operative photograph (C).
147FF7.jpg|Fig. 147.7 Z-plasties in transposition flaps. Z-pl
asties are highlighted within the designs of both the rhombic and the bilobed tr
ansposition flap. Note in the rhombic flap the middle arm of the Z-plasty is lin
e B and is the direction of anticipated tissue lengthening. In the bilobed trans
position flap diagram, there is a series of three Z-plasties all contributing to
tissue gain in the desired direction of the defect.
147FF8.jpg|Fig. 147.8 Classic Z-plasty. A Defect on nasal tip
adjacent to the free margin of the ala. B,C Bilobed flap reconstruction
with minimal distortion of the alar rim and long term result.
147FF9.jpg|Fig. 147.9 Rotation flap. Large defect (A)
on the medial cheek and lower eyelid reconstructed with a rotation flap (Mustard
e flap) with displacement of the superior Burow's triangle laterally along the c
urvilinear tangent which follows the relaxed skin tension lines (B). Fina
l results with no distortion of the eyelid and incision lines nicely camouflaged
along cosmetic subunit borders and relaxed skin tension lines (C).
147FF10.jpg|Fig. 147.10 Single tangent advancement flap. A La

rge defect situated between the ear and the eye. B A single tangent advan
cement flap (Burow's flap) reconstructs the defect by displacing a Burow's trian
gle inferiorly to just below the earlobe. C One month after reconstructio
n.
147FF11.jpg|Fig. 147.11 Double tangent advancement flap. This
technique was used to reconstruct and preserve the continuity of the eyebrow in
this patient.
147FF12.jpg|Fig. 147.12 Retroauricular flaps. A Vascular pedi
cle derived immediately beneath the island of skin. B Depicts the vascula
r pedicles deriving from tissue lateral to the island flap.
147FF13.jpg|Fig. 147.13 Island pedicle flap. Reconstruction o
f a nasal defect with an island pedicle flap whose pedicle is derived deep to th
e island along the alar crease.
147FF14.jpg|Fig. 147.14 Island pedicle flap. A Large forehead
defect. B Intraoperative photograph of a lateral pedicle island flap dem
onstrating the single pedicle which is based inferior to the flap on the rich bl
ood supply of the supratrochlear and supraorbital arteries.
147FF15.jpg|Fig. 147.15 Island pedicle flap. A Demonstration
of the reconfiguration of defect (shaded area) to defect in B. Shaded sec
ondary defect in B is comprised entirely of acute angles which are easily closed
primarily.
147FF16.jpg|Fig. 147.16 Island pedicle flap. A side view of a
defect and an island pedicle flap. The plane of rotation is perpendicular to th
e skin surface. The cross-hatched shaded area is where the equivalent of a Burow
's triangle has been removed to facilitate flap movement. The dotted line is ana
logous to the back cut of a rotation flap. Note similarities between a rotation
flap and an island pedicle flap.
147FF17.jpg|Fig. 147.17 The variants of the rhombic flap. A T
he Lindberg flap which is the standard rhombic flap. B The modifications
of Defourmental. C The Webster 30° modification of the rhombic flap.
147FF18.jpg|Fig. 147.18 Rhombic transposition flap. Clinical
example of a rhombic flap on the upper lateral nose.
147FF19.jpg|Fig. 147.19 Bilobed flap. A Depicts the tradition
al design of the bilobed flap resulting in tissue protrusion at the pivot point.
B Modifications of the bilobed flap as described by Zitelli.
147FF20.jpg|Fig. 147.20 Bilobed flap. A distal nose defect re
constructed with a modified bilobed transposition flap.
147FF21.jpg|Fig. 147.21 Melolabial transposition flap. A Larg
e nasal defect involving loss of cartilage and extending to the intranasal skin.
B Reconstruction with a nasolabial transposition flap after insertion of
a cartilage strut which was placed parallel to the alar rim in order to reconst
itute the structural integrity of the nose. The flap is wrapped around the alar
rim and folded onto itself reforming the rim.
147FF22.jpg|Fig. 147.22 Paramedian forehead flap. A Large ful
l thickness defect of the right half of the distal nose. The mucosal defect was
reconstructed with a contralateral septal mucosal pull through flap. A 15 m
m square cartilage graft was harvested from the nasal septum and used to reconst
itute the structural integrity of the nasal sidewall. Note that the remainder of
the nasal sidewall cosmetic subunit and the right nasal tip subunit will be exc
ised and reconstructed with a forehead flap. B Immediately post-operative
. C Immediately after takedown of flap 3 weeks later. D Early cosm
etic results with no revision 2 months post-operative.
147FF23.jpg|Fig. 147.23 Melolabial interpolation flap. A Larg
e alar defect with severe loss of structural integrity. B Nasolabial inte
rpolation flap in place. C Long-term cosmetic and functional results.
147FF24.jpg|Fig. 147.24 Retroauricular flap. A Large helical
rim defect with preservation of much of the auricular cartilage. B Poster
ior ear defect and the planned incisions for the retroauricular flap. C R
etroauricular flap in place immediately post-operative. D Immediately aft
er takedown.
147FF25.jpg|Fig. 147.25 Spear's flap. A Nasal defect involvin
g the entire nasal ala and a portion of the nasal sidewall with the plans marked
for a nasolabial transposition flap with a twist as described by Spear. B Flap in place having been twisted on a subcutaneous pedicle sutured into the m
ucosal side of the defect and folded upon itself followed by suturing of the cut
aneous side of the defect. C Early results after second revision.
147FT1.jpg|Table 147.1 STARTS mnemonic.
147FT2.jpg|Table 147.2 Classification of flaps based on design ch
aracteristics.
147FT3.jpg|Table 147.3 Variations in preferred flap location.
148FF1.jpg|Fig. 148.1 Graft types for soft tissue reconstruction.

148FF2.jpg|Fig. 148.2 Full thickness skin graft. A Full thick
ness skin graft taken from the preauricular region was used to repair this defec
t of the right upper anterior ear. B Eight-week postoperative result.
148FF3.jpg|Fig. 148.3 Placement of a full thickness skin graft. A
 1.7 × 2.0 cm defect of the nasal tip is present after removal of
recurrent basal cell carcinoma with Mohs micrographic surgery. A preauricular do
nor site provides the best match in this case for color, sebaceous quality, degr
ee of photodamage, and thickness. B After marking the periphery of the re
cipient site with a marking pen, the template material is pressed against the de
fect. The resulting outline of the inked margin serves as a guide to cut a perfe
ct template, seen here adjacent to the nasal defect. C The template has b
een applied to the preauricular donor site, and inking material applied around i
t. Burow's triangles are outlined on either side of the template to close the si
te primarily. Marking the donor site prior to local anesthesia prevents incorrec
t sizing due to tissue stretch from lidocaine infiltration. D The graft i
s carefully defatted with curved iris scissors so that only the white, glistenin
g surface of the dermis remains. E Preauricular donor site is closed prim
arily. F Full thickness skin graft is trimmed with curved iris scissors t
o ensure a perfect fit. G Full thickness skin graft sewn into place with
6-0 fast-absorbing chromic gut sutures. H Xeroform bolster sewn into plac
e over full thickness skin graft with 5-0 polypropylene tie-over sutures.
148FF4.jpg|Fig. 148.4 Split thickness skin graft site on the fore
head one year after placement. Note hypopigmentation and smooth texture of g
rafted skin compared with the surrounding normal skin.
148FF5.jpg|Fig. 148.5 Freehand harvesting of a small split thickn
ess skin graft from the upper outer arm using a #15 scalpel blade. The blade
is oriented parallel to the skin, and gently swept just below the level of the
epidermis, so that the blade is just visible beneath the graft. An assistant app
lies traction to the donor site to facilitate harvesting.
148FF6.jpg|Fig. 148.6 Harvesting of a large split thickness skin
graft with an electric dermatome. A As the Zimmer air dermatome glides over
the donor skin, the graft emerges from the pocket area of the dermatome, and is
lifted away from the machine with sterile hemostats. B Split thickness sk
in graft placed on sterile saline-soaked gauze. Note that the edges curl inward
toward the dermal surface of the graft. C An Opsite® dressing is pla
ced over the donor site on the anterior thigh immediately after harvesting.
148FF7.jpg|Fig. 148.7 Technique of interlocking composite graft p
lacement. Repair of a full thickness nasal alar defect extending through bot
h skin and cartilage. A Donor site at the crus of the helix. An area of s
kin approximately 5–10% greater in area than the actual defect is marked o
ut, with cartilaginous wings marked out on either side. After the graft is harve
sted, the skin is removed on both sides to expose the cartilaginous portion of t
he graft, such that two cartilaginous pegs with their overlying perichondrium fr
ame the lateral aspects of the graft. B A pocket is undermined on either
side of the recipient site, into which the cartilaginous pegs will be placed. C The cartilaginous pegs are inserted into the holes prepared within the al
ar tissue on either side of the defect. The graft is then sutured into place.
148FF8.jpg|Fig. 148.8 Harvesting and placement of a free cartilag

e graft. A The posterior conchal bowl donor site has been incised to the lev
el of the perichondrium. The desired length of cartilage was incised with the sc
alpel, and a second incision made parallel to the first to isolate a cartilagino
us strip with its overlying perichondrium. B The ends of the cartilaginou
s strip with its overlying perichondrium have been inserted into pockets undermi
ned on either side of the recipient bed, such that the graft interlocks with its
recipient bed on the left nasal ala. The graft is sutured to the underlying der
mis with one 5-0 absorbable suture for additional security. C A full thic
kness skin graft has been sutured into place over the free cartilage graft. D
& E Eight-week postoperative front and side views of the full thickness
skin graft and underlying free cartilage graft on the left nasal ala. The alar
rim remains in perfect alignment.
148FT1.jpg|Table 148.1 Comparison of graft types used in soft tis
sue reconstruction
148FT2.jpg|Table 148.2 Causes of graft failure
148FT3.jpg|Table 148.3 Donor site considerations for full thickne
ss skin grafts
148FT4.jpg|Table 148.4 Summary of possible full thickness donor s
ites for defects in different locations
148FT5.jpg|Table 148.5 Classification of split thickness skin gra
fts (in inches)
149FF1.jpg|Fig. 149.1 Surgical anatomy of the nail unit.
149FF2.jpg|Fig. 149.2 Relationship of nail matrix and surface. The proximal part of the nail matrix forms the superficial (dorsal) nail surfa
ce; the distal portion of the matrix forms the inferior (ventral) portion. Hence
, surgery to the distal matrix is preferable to surgery of the proximal matrix b
ecause, if there is scarring, it will be on the under surface of the nail and th
erefore less obvious.
149FF3.jpg|Fig. 149.3 The location of lidocaine injections for wi
ng block and digital block.
149FF4.jpg|Fig. 149.4 Sterile glove used as a tourniquet and ster
ile field.
149FF5.jpg|Fig. 149.5 Instruments used in nail surgery. Note
the double–action nail nipper and Freer elevator on the left side of the t
ray.
149FF6.jpg|Fig. 149.6 English nail splitter is used to divide the
nail plate prior to partial nail avulsion. A Note the flat, anvil-like blad
e of the English nail splitter that is inserted under the nail plate. B A
fter partial nail avulsion, a glomus tumor is excised.
149FF7.jpg|Fig. 149.7 Nail plate avulsion. A The Freer elevat
or is inserted under the nail plate in several parallel passes. B The loo
sened nail plate is grabbed with a hemostat and removed.
149FF8.jpg|Fig. 149.8 Proximal nail plate avulsion. A, B The
Freer elevator is inserted under the proximal portion of the nail plate and rota
ted to lift the thickened nail plate from the nail bed.
149FF9.jpg|Fig. 149.9 Nail matrix exploration. A After nail p
late avulsion, releasing incisions in the proximal nail fold are made. B
The PNF is retracted with skin hooks or sutures to allow visualization of the na
il matrix. C The PNF is replaced and sutured or approximated with steri s
trips.
149FF10.jpg|Fig. 149.10 Orientation of biopsy/excision in the nai
l unit.
149FF11.jpg|Fig. 149.11 Nail fold biopsy of a space occupying les
ion. A Free relevator is inserted beneath the proximal nail fold and a cresc
ent of nail fold is removed.
149FF12.jpg|Fig. 149.12 Nail bed excision of a glomus tumor. A Elliptical excision is oriented longitudinally. B Absorbable sutures ap
proximate the wound edges.
149FF13.jpg|Fig. 149.13 Nail matrix biopsy can result in permanen
t nail dystrophy. Taking the specimen from the distal nail matrix, if possib
le, and suturing the defect minimize scarring.
149FF14.jpg|Fig. 149.14 Nail matrix excision in the distal matrix
. The excision is oriented in the horizontal axis in the matrix and sutured.
149FF15.jpg|Fig. 149.15 Lateral longitudinal biopsy. The late
ral portions of the nail unit are excised en bloc including the hyponychi
um, nail plate, nail bed, nail matrix and proximal nail fold.
149FF16.jpg|Fig. 149.16 Phenol matrixectomy for ingrown toenails.
 Part or all of the nail plate is avulsed and full strength phenol on a smal
l cotton wisp on a toothpick is inserted under the nail fold and applied to the
nail matrix.
149FT1.jpg|Table 149.1 Prerequisites for successful nail surgery
or nail biopsy.
149FT2.jpg|Table 149.2 Patient evaluation prior to nail surgery.
149FT3.jpg|Table 149.3 Clinical features of nail bed disorders in
which a biopsy may facilitate diagnosis and treatment. Adapted from Rich P.
Nail biopsy: indications and methods. JDSO. 1992;18:673–82
149FT4.jpg|Table 149.4 Nail unit tumors: radiographic findings an
d surgical treatments. Modified from Rich L, Curr Prob Dermatol. 1999; 11:16
1–208.
149FT5.jpg|Table 149.5 Etiologies of a pseudo-Hutchinson’s
sign.Adapted from Baran R. Hutchinson’s sign: a reappraisal. J Am Acad
Dermatol. 1996;34:87–90.
150FF1.jpg|Fig. 150.1 Pathologic examination of tissue margins. Comparison of traditional ‘breadloaf’ sections (0.1% of total mar
gin examined) versus Mohs micrographic surgery (100% of total margins examined).
150FF2.jpg|Fig. 150.2 Mohs micrographic surgery technique. Pr
eparation of layer including: excision of layer, orientation, mapping and prepar
ation of frozen sections.
150FF3.jpg|Fig. 150.3 Mohs micrographic surgery technique. A
Debulking of tumor with curette. B The scalpel is held at a 45° angl
e away from the tumor in order to create a bevelled incision. C Hash mark
s are placed and excision is completed.
150FT1.jpg|Table 150.1 Indications for Mohs surgery.
150FT2.jpg|Table 150.2 Cutaneous tumors manageable with Mohs surg
ery.
150FT3.jpg|Table 150.3 Preoperative considerations for Mohs surge
ry.
150FT4.jpg|Table 150.4 Guidelines for antibiotic prophylaxis for
the prevention of endocarditis and prosthesis infection during Mohs surgery.
150FT5.jpg|Table 150.5 Management of blood thinners during Mohs s
urgery.
151FF1.jpg|Fig. 151.1 Interrelated surgical complications.
151FF2.jpg|Fig. 151.2 Algorithms generated from preoperative ques
tionnaire. (PABA, para-aminobenzoic acid.)
151FF3.jpg|Fig. 151.3 Placement of Penrose drain because of exces
sive bleeding.
151FF4.jpg|Fig. 151.4 Postoperative appearance of wound closed un
der tension with resulting necrosis.
151FF5.jpg|Fig. 151.5 Motor nerve danger areas.
151FF6.jpg|Fig. 151.6 Damage to the facial nerve. A Loss of t
he ability to elevate the forehead due to transection of the temporal branch. B Loss of function of the main branch of the facial nerve. The ability to c
lose the eye has been restored by the placement of a gold weight in the eye lid.
151FF7.jpg|Fig. 151.7 ‘Trap-door’ or ‘pin-cushi
on’ appearance of a flap reconstruction.
151FF8.jpg|Fig. 151.8 Hematoma. A Postoperative hematoma form
ation. B Evacuation of hematoma.
151FF9.jpg|Fig. 151.9 Organized hematoma.
151FF10.jpg|Fig. 151.10 Wound infection and necrosis at full-thic

kness skin graft site.
151FF11.jpg|Fig. 151.11 Contact dermatitis to antibiotic ointment
.
151FF12.jpg|Fig. 151.12 Inflammatory suture reaction.
151FF13.jpg|Fig. 151.13 Necrosis of a full-thickness skin graft. Two weeks after placement.
151FF14.jpg|Fig. 151.14 Tensile strength of skin post incision.
151FF15.jpg|Fig. 151.15 Wound dehiscence after suture removal.
151FF16.jpg|Fig. 151.16 Granulomatous reaction to suture placemen
t.
151FF17.jpg|Fig. 151.17 Suture ‘tracks’ in a spread s
car.
151FF18.jpg|Fig. 151.18 Hypertrophic scar. One month after ex
cisional surgery.
151FT1.jpg|Table 151.1 Wound classification1.
151FT2.jpg|Table 151.2 Recommendations for prophylaxis21</su
p>.
152FF1.jpg|Fig. 152.1 The Glogau wrinkle scale. A Type I (&#8
216;no wrinkles’): skin is uniform in color. There is an absence of lines
event at the corners of the eyes and mouth. B Type II (‘wrinkles in
motion’): when the face is at rest, the patient appears similar to type I
. But when the face is animated by expression, there are many parallel lines whi
ch appear, first at the corners of the mouth, then parallel to the nasolabial fo
lds, then at the corners of the eyes, and finally over the malar cheeks. C Type III (‘wrinkles at rest’): this patient clearly shows the para
llel lines seen with animation in type II except they are now present with the f
ace at complete rest. D Type IV (‘only wrinkles’): the perior
al skin in particular is likely to demonstrate the total replacement of normal s
kin with minute, rhomboid and geometric rhytids, clearly seen in this patient. T
he entire face shows similar rhytids on close inspection.
152FF2.jpg|Fig. 152.2 Laser resurfacing. This patient has und
ergone laser resurfacing to her full face. She looks ‘better’ but no
t ‘younger’, because no attention has been paid to volume changes.
152FT1.jpg|Table 152.1 Glogau photoaging classification – w
rinkle scale
152FT2.jpg|Table 152.2 Relationship of emotion states with brow p
ositions
153FF1.jpg|Fig. 153.1 The iron oxide particles in facial foundati
on tend to migrate to the follicular ostia as sebum and eccrine secretions mix w
ith the cosmetic film.
153FF2.jpg|Fig. 153.2 A 400x video microscope captures the appear
ance of the light reflective particles and pigment particles following applicati
on of a blush to the cheeks.
153FF3.jpg|Fig. 153.3 Upper eyelid dermatitis may be exacerbated
by the use of heavily pigmented, light reflective eye shadows.
153FF4.jpg|Fig. 153.4 The chemical structure of glycolic acid acc
ounting for its hydrophilic properties.
153FF5.jpg|Fig. 153.5 The chemical structure of salicylic acid ac
counting for its lipophilic properties.
153FT1.jpg|Table 153.1 Categories of cleansing product.
153FT2.jpg|Table 153.2 Specialty soap formulations.
153FT3.jpg|Table 153.3 Functions of facial foundation.
153FT4.jpg|Table 153.4 Covering ability of face powder ingredient
s. *Listed in order of increasing opacity.
153FT5.jpg|Table 153.5 Pigments allowed by the US FDA in eye shad
ow cosmetics.
153FT6.jpg|Table 153.6 Camouflage for abnormalities of facial pig
mentation.
153FT7.jpg|Table 153.7 Shampoo detergents.
153FT8.jpg|Table 153.8 Specialty shampoos.
153FT9.jpg|Table 153.9 Hair conditioners.
153FT10.jpg|Table 153.10 Nail cosmetics.
153FT11.jpg|Table 153.11 Nall sculpture application.
153FT12.jpg|Table 153.12 Dermatologic uses of hydroxy acids as to
pical preparations and peels.
154FF1.jpg|Fig. 154.1 UV attenuation by scattering. Many inci
dent UV photons are reflected back into the environment before striking the skin
.
154FF2.jpg|Fig. 154.2 UV attenuation by absorption. Many inci
dent UV photons are absorbed before striking the skin and re-emitted as infrared
(IR).
154FF3.jpg|Fig. 154.3 Maximum allowable concentrations of common
active ingredients in US sunscreen preparations. Proposed final FDA rule for
sunscreens .
154FF4.jpg|Fig. 154.4 Reletive attenuation of wavelengths by the
atmosphere.
154FF5.jpg|Fig. 154.5 Surface irradiance in the UV range.
155FF1.jpg|Fig. 155.1 Cleansing and degreasing the face. A Ir
regular surface. B Clean, regular surface.
155FF2.jpg|Fig. 155.2 Levels of frosting. A Level I frosting
as found with light chemical peeling; erythema with streaky frosting. B L
evel II frosting: erythema with diffuse white frosting. C Level III frost
ing: solid white enamel frosting.
155FF3.jpg|Fig. 155.3 Salicylic acid peels. These peels are e
ffective for the treatment of acne and comedones. Repetitive treatment over 6 we
eks with acne treatment will hasten resolution of the condition. Note the perifo
llicular frosting seen with salicylic acid, a lipophillic chemical.
155FF4.jpg|Fig. 155.4 Medium depth chemical peel used to treat mo
derate photoaging skin. A Preoperative demonstrating epidermal growths with
aging textural changes. B Application of 35% TCA directly after Jessner's
solution. C White enamel frosting (level III) from 35% TCA. D Des
quamation and inflammation 4 days after peel. E Final results 6 months la
ter.
155FF5.jpg|Fig. 155.5 Post-inflammatory hyperpigmentation unrespo
nsive to hydroquinone, tretinoin and superficial chemical peeling. Full resp
onse to medium depth chemical peel and topical agents. A Preoperative. B Six weeks postoperative.
155FF6.jpg|Fig. 155.6 Combination procedure utilizing perioral &#
8211; periorbital CO2 laser resurfacing with Jessner's + 35% TCA peel
over remaining face. The peel will blend color and texture of the laser tre
ated areas. A Preoperative: the eyelids and lips need deeper resurfacing
than cheeks, which require only medium depth injury. B Four days postoper
ative: note difference in rate of healing between laser and peel treated areas.
C One year postoperative.
155FF7.jpg|Fig. 155.7 Technical aspects of the Jessner's + 35% TC
A peel. A Appearance of level I frosting after application of Jessner's solu
tion, erythema with blotchy frosting. B 35% TCA applied after Jessner's s
olution dries with an even application using cotton tip applicators, one to four
. A level III or white enamel frosting is obtained. C Eyelids are treated
with one cotton tip applicator moistened with 35% TCA. A dry applicator is used
to absorb tears during eyelid peeling. D Lip rhytides are peeled with sa
turated cotton tip applicators. The wooden shaft is used to rub peel solution fu
rther in to the lip rhytides.
155FF8.jpg|Fig. 155.8 Advanced photoaging of perioral rhytides tr
eated with Baker's Phenol peel. A Preoperative demonstrating perioral rhagad
es, textural and pigmentary changes with epidermal growths. B Postoperati
ve: 2 years later. Note the phenol peel maintains correction for many years.
155FF9.jpg|Fig. 155.9 Complications from Baker's phenol peel.

There was prolonged nonhealing resulting in hypopigmentation and marbled scarri
ng.
155FF10.jpg|Fig. 155.10 Microdermabrasion. Aluminum oxide cry
stals are propelled at high speeds within a closed system and removed with sucti
on.
155FF11.jpg|Fig. 155.11 Dermasanding. Manual dermasanding uti
lizing 320 grit silicone carbide sandpaper to blend CO2 laser resurfa
cing into eyebrow area.
155FF12.jpg|Fig. 155.12 Mechanical dermabrasion. This techniq
ue is performed with a diamond fraize over rigid skin cooled with a topical refr
igerant spray.
155FF13.jpg|Fig. 155.13 Full face dermabrasion performed for acne
scars. A Preoperative: shallow and atrophic scars most amenable to dermabra
sion. B Postoperative: dermabrasion prior to biosynthetic dressing. C Three month postoperative.
155FT1.jpg|Table 155.1 Classification of ablative skin resurfacin
g methods. Although this classification represents an oversimplification bec
ause the depth of injury actually varies somewhat along a continuum for each dif
ferent type of resurfacing procedure, it is helpful when discussing the various
options with a patient.
155FT2.jpg|Table 155.2 Major indications for chemical and mechani
cal skin resurfacing.
155FT3.jpg|Table 155.3 Contraindications to chemical and mechanic
al skin resurfacing. *These contraindications apply only to medium-depth and
deep resurfacing procedures.
155FT4.jpg|Table 155.4 Jessner’s solution (Combes’ fo
rmula).
155FT5.jpg|Table 155.5 The Baker-Gordon formula.
155FT6.jpg|Table 155.6 Advantages of manual dermasanding over mot
orized dermabrasion.
155FT7.jpg|Table 155.7 Conditions for which motorized dermabrasio
n may be the preferred resurfacing modality
156FF1.jpg|Fig. 156.1 Anatomic representation of the venous syste
m. The deep venous system drains the superficial venous system, which, in tu
rn, is fed from the skin surface by telangiectasias in the dermis, which drain v
ia reticular veins into the larger venous channels located in the reticular derm
is and subcutaneous compartments.
156FF2.jpg|Fig. 156.2 Superficial venous system. Lateral and
medial views of the distribution of the major axial trunks of the superficial ve
nous system, the reater and lesser saphenous veins, and associated tributaries.
156FF3.jpg|Fig. 156.3 Deep venous system. The major drainage
vessel below the knee is the popliteal vein, while the femoral vein is the major
portal of drainage in the inguinal area of the groin (greater saphenous distrib
ution).
156FF4.jpg|Fig. 156.4 The muscle pump, or ‘peripheral heart
’. This is located primarily in the calves. During muscle contraction,
compression of veins transports blood to the heart by means of the deep venous
system.
156FF5.jpg|Fig. 156.5 Doppler examination. A Doppler probe he
ld at a 30° to 45° angle. B Doppler examination of the greater
saphenous vein; a reflux found after the release of distal compression denotes v
enous valvular insufficiency.
156FF6.jpg|Fig. 156.6 Mechanisms of action of sclerosing solution
s. A Detergent; B Hypertonic; C Chemical.
156FF7.jpg|Fig. 156.7 Air bolus technique. Injection of an ai
r bolus (0.5 ml) prior to injection of sclerosant can ensure intravascular
needle location; perivascular tissue blanching is seen if extravasation has occu
rred.
156FF8.jpg|Fig. 156.8 Treatment of arborizing feeder veins. T
his therapeutic approach (arrow) diminishes the number of injections required in

a given sclerotherapy treatment session, thus minimizing potential side effects
.
156FF9.jpg|Fig. 156.9 Marking of treatment sites. Prior to la
rge-vein sclerotherapy, marking of treatment sites in a standing position by ind
elible marker is performed.
156FF10.jpg|Fig. 156.10 Doppler-guided sclerotherapy. Doppler
-guided injection is carried out 1 cm distal to point of reflux as ascertai
ned by Doppler examination.
156FF11.jpg|Fig. 156.11 Sclerotherapy-induced hyperpigmentation.
A Sclerotherapy-induced hyperpigmentation diffusely distributed along the en
tire treated vessel. B Fading of pigmentation at 1 month. C Total
resolution of postsclerotherapy hyperpigmentation at 12 months, which occurs in
98–99% of cases.
156FF12.jpg|Fig. 156.12 Post-sclerotherapy necrotic ulceration fo
llowing extravasation of hypertonic saline.
156FF13.jpg|Fig. 156.13 Hooking venous segments. A After hook
ing, the vein is clamped proximately and distally, it is then pulled and rolled
to free it from surrounding connective tissue adventitial attachment. B S
uccessive clamping of the hooked vessel with a concomitant pushing or pulling mo
tion allows avulsion of longer venous segments.
156FF14.jpg|Fig. 156.14 Insertion of the diode laser fiber (815&n
bsp;nm) into the greater saphenous vein under duplex guidance.
156FF15.jpg|Fig. 156.15 The Closure® system utili
zes either the 5 Fr or 8 Fr catheter to deliver radiofrequency energy
to the greater saphenous vein wall.
156FT1.jpg|Table 156.1 Indications for vascular testing.
156FT2.jpg|Table 156.2 Comparison of Doppler ultrasound and duple
x scanning for presclerotherapy evaluation.
156FT3.jpg|Table 156.3 A guide for the selection of sclerosing so
lution concentration and volume by vessel type.
156FT4.jpg|Table 156.4 Important characteristics of sclerosing so
lutions.
156FT5.jpg|Table 156.5 Classification of veins and clinical appro
ach to treatment of venous pathology.
156FT6.jpg|Table 156.6 Sclerotherapy complications.
156FT7.jpg|Table 156.7 Ways to minimize post-sclerotherapy hyperp
igmentation.
156FT8.jpg|Table 156.8 Complications of ambulatory phlebectomy.
157FF7.jpg|Fig. 157.7 The patient's vantage point. This is di
fferent from the physician's vantage point, since she is looking down at her own
areas of adiposity.
157FF9.jpg|Fig. 157.9 A variety of small diameter liposuction can
nulas. Courtesy of WP Coleman III, MD.
157FF10.jpg|Fig. 157.10 Reciprocating powered cannula. A reci
procating powered cannula with a 3 mm to and fro motion. Courtesy of the Dermato
logic Surgery.
157FF11.jpg|Fig. 157.11 Powered liposuction. Using powered li
posuction to more precisely sculpt small areas of fat around the umbilicus.
157FF12.jpg|Fig. 157.12 Contraction of the fatty layer. A Imm
ediately after liposuction, the fatty layer resembles a wet sponge. With subsequ
ent subtraction of the fat cells, the thickness of the subcutaneous tissue decre
ases. B Much like a dry sponge, the subcutaneous tissue has compacted.
157FT1.jpg|Table 157.1 Formula for tumescent liposuction (lidocai
ne 0.05%, epinephrine 1:1 000 000).
158FF1.jpg|Fig. 158.1 The microscope. Meij, EMT and stereomic
roscope shown mounted on a backlight dissection box.
158FF2.jpg|Fig. 158.2 Metabolism of testosterone. Testosteron
e is metabolized into dihydrotestosterone (DHT) by the enzyme 5α-reductase.
158FF3.jpg|Fig. 158.3 Androgenetic alopecia.

158FF4.jpg|Fig. 158.4 Norwood classification of male pattern bald
ness.
158FF5.jpg|Fig. 158.5 Medical treatment. Finasteride versus place
bo clinical trial. The figure shows the difference in hair count after 5 yea
rs.
158FF6.jpg|Fig. 158.6 Medical consultation for hair transplant.
158FF7.jpg|Fig. 158.7 The natural hairline. The photograph sh
ows the natural hairline of a 32-year-old Caucasian male.
158FF8.jpg|Fig. 158.8 Follicular unit count per cm2. The photograph demonstrates the differences between 35, 40 and 45 follicular
units/cm2 (left to right).
158FF9.jpg|Fig. 158.9 Maximizing recipient density. Before (A, C) and after (B, D) photos of patients following a single transp
lant session.
158FF10.jpg|Fig. 158.10 Hair densitometer. The Welch-Allyn de
rmatoscope was modified with an attachment to produce a 0.25 cm2
grid. This unit is called a trichoscope and is excellent for measuring donor ha
ir density.
158FF11.jpg|Fig. 158.11 Donor strip harvesting. A The donor s
trip prior to closure. B The donor area closure with staples.
158FF12.jpg|Fig. 158.12 Technique for graft slivering. A Donor slivering producing slivers 2 mm wide by 10 mm long. B
Slivers being sectioned into follicular units. C Follicular unit grafts
are placed into saline dish and separated into one, two and three-haired follicu
lar units.
158FF13.jpg|Fig. 158.13 Graft dissection. The follicular unit
s are stored in isotonic saline to maintain viability.
158FF14.jpg|Fig. 158.14 Recipient site. Comparison of an 18-g
auge recipient site versus an 19-gauge recipient site.
158FF15.jpg|Fig. 158.15 Insertion phase: planting front to back. Planting grafts from front to back.
158FF16.jpg|Fig. 158.16 A 40-year-old man with Norwood IV pattern
alopecia. The patient underwent a total of 2500 grafts; the patient's verte
x was not transplanted. This patient's hairline was started in 1994 and complete
d in 1997.
158FF17.jpg|Fig. 158.17 A 62-year-old man with Norwood VI pattern
alopecia. The same patient is shown after receiving 3500 grafts. The final
hairline was deliberately made irregular with a 2 cm feathering zone.
158FT1.jpg|Table 158.1 Five basic criteria for assessing
158FT2.jpg|Table 158.2 Racial variation in follicular units. Repr
oduced with permission from Dermatologic Surgery, The Distribution of Follicular
Units in the Chinese Scalp: Implications for Reconstruction of Natural-Appearin
g Hairlines in Orientals, Ren-Yeu Tsai, MD, et al, Vol. 28., No. 6., pgs. 500&#8
211;503, June 2002.
158FT3.jpg|Table 158.3 Comparison of simultaneous versus separate
d needle stick and graft placement techniques. Reproduced with permission fr
om Hair Restoration and Laser Hair Removal – Dermatologic Clinics, W. B. S
aunders Company, Methodology of Follicular Unit Hair transplantation, Dow Stough
, MD, Jeffrey Whitworth, MD, Vol. 17, No. 2, 1999, pp. 297–306.
158FT4.jpg|Table 158.4 Post-operative instructions. Special consi
derations following hair transplantation surgery.
159FF1.jpg|Fig. 159.1 Soft tissue augmentation placement.
159FF2.jpg|Fig. 159.2 Bovine collagen – lip augmentation. Pre- (A) and post-injection (B) of 1 cc of Zyplast® i
nto the vermilion of the lips for augmentation.
159FF3.jpg|Fig. 159.3 Bovine collagen – adverse reactions. Excess ecchymosis resulting from injection of Zyplast® with serial punc
ture technique into the nasolabial folds of a patient on anticoagulation therapy
.
b>. Despite two negative skin tests, a granulomatous hypersensitivity reaction o
ccurred following Zyderm I® injections into the periocular rhytides.
b>. Sterile abscesses appeared in the nasolabial folds following injection of Zy
plast®. The patient had two prior negative skin tests. Resolution was not c
omplete for 12 months.
159FF6.jpg|Fig. 159.6 Human-derived collagen. Pre- (A)
and postoperative (B) appearance following injection of 1 ml of Der
malogen® into each nasolabial fold.
159FF7.jpg|Fig. 159.7 Expanded polytetrafluoroethylene. Extru
sion and infection of SoftForm® in the glabellar region.
159FF8.jpg|Fig. 159.8 Expanded polytetrafluoroethylene. Super
ficial placement of SoftForm® is both palpable and visible.
159FF9.jpg|Fig. 159.9 Lipotransfer. Photographs before and af
ter injection of 10 cc of autologous fat into the buccal area.
159FF10.jpg|Fig. 159.10 Lipotransfer. Photographs before and
after injection of approximately 10 ml of autologous fat into the dorsum of
each hand.
159FF11.jpg|Fig. 159.11 Lipotransfer. Intravascular injection
of autologous fat required surgical evacuation.
159FT1.jpg|Table 159.1 Causes of cutaneous defects.
159FT2.jpg|Table 159.2 Soft tissue augmentation: preinjection con
siderations.
159FT3.jpg|Table 159.3 Soft tissue augmentation indications.
159FT4.jpg|Table 159.4 Historical milestones of filler substances
.
159FT5.jpg|Table 159.5 Partial list of characteristics of the ide
al filler substance.
159FT6.jpg|Table 159.6 Complications associated with use of bovin
e collagen.
159FT7.jpg|Table 159.7 Benefits of hyaluronic acid derivatives.
159FT8.jpg|Table 159.8 Soft tissue filler substance efficacy.
159FT9.jpg|Table 159.9 Soft tissue filler substance efficacy.
159FT10.jpg|Table 159.10 Practical and theoretical questions rela
ted to adipocyte viability in lipotransfer.
159FT11.jpg|Table 159.11 Partial list of filler substances.
160FF1.jpg|Fig. 160.1 Equipment. A 30 gauge insulin needle ha
s no ‘dead volume’ and is ideal for injections.
160FF2.jpg|Fig. 160.2 Frown lines in the glabellar region. Th
e frown lines are caused by contraction of the corrugator, orbicularis, procerus
, and depressor supercilii muscles.
160FF3.jpg|Fig. 160.3 Blepharoptosis. Diffusion of toxin to t
he levator of the upper eyelid resulted in eyelid ptosis (subject's left eye).
160FF4.jpg|Fig. 160.4 Injection sites for glabellar frown lines. The authors currently use seven injection sites when treating glabellar frow
n lines and vary the dosage depending on the individual brow.
160FF5.jpg|Fig. 160.5 Glabellar lines. In a subject at rest (
A) and during frowning (B). Subject at rest (C) and attempt
ing to frown (D) one week after BOTOX® treatment.
160FF6.jpg|Fig. 160.6 Crow's feet. Subject with crow's feet b
efore (A) and 3 weeks after BOTOX® treatment (B).
160FF7.jpg|Fig. 160.7 Horizontal forehead lines produced when
the subject elevated the brows before (A) and one month after BOTOX
® treatment (B).
160FF8.jpg|Fig. 160.8 Hypertrophic orbicularis. BOTOX&#1
74; treatment of the lower pretarsal orbicularis opens the palebral apertu
re. Note the position of the lower eyelids in the subject before (A) and
after treatment (B).

160FF9.jpg|Fig. 160.9 Mouth frown. The subject before (A) and after BOTOX® treatment (B) of the depressor angul
i oris.
160FF10.jpg|Fig. 160.10 Mental crease. Treatment of traumatic
ally damaged mentalis. (A, B) Subject puckers before treatment. (C, D) Two weeks after chemodenervation of the mentalis with BOTOX®.
160FF11.jpg|Fig. 160.11 Platysmal bands. Before (A) an
d after (B) BOTOX® treatment. Photographs courtesy of M.
Carney.

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0FF1.jpg|<b>Fig. I.1</b>&nbsp;<b>Macule.

</b> Congenital white macule of nevus de

the Kimball Art Museum, Fort Worth, Texas.

Application of contact allergens (Ag) into a sensitized individual causes the re

ng dermatosis admixed with the scratch marks.

st. Courtesy of Ron Rapini, MD.

9FF20.jpg|<b>Fig. 9.20</b>&nbsp;<b>Microabscess of Munro</b>. Remnants of neutro

d transitional role of clonal dermatitis in the evolution of mycosis fungoides.<

blind studies; (2) clinical series; (3) anecdotal.

phase, dendritic cells present self-peptides modified by exogenous antigens (vir

12FF22.jpg|<b>Fig. 12.22</b>&nbsp;<b>Chronic sclerodermoid graft-versus-host dis

particularly in combination with IFN&#947;, promotes production of chemokines su

14FF2.jpg|<b>Fig. 14.2</b>&nbsp;<b>Adult seborrheic dermatitis of the face and s

15FF14.jpg|<b>Fig. 15.14</b>&nbsp;<b>Allergens being marked upon removal of Scan

17FF4.jpg|<b>Fig. 17.4</b>&nbsp;<b>Initial subclinical response to tissue pertur

18FT3.jpg|<b>Table 18.3</b>&nbsp;<b>The most common plants causing toxin-mediate

e of an intradermal injection of autologous serum, but not at that of a normal s

22FF7.jpg|<b>Fig. 22.7</b>&nbsp;<b><i>In vitro</b> inhibition of Fas-mediated ke

23FF14.jpg|<b>Fig. 23.14</b>&nbsp;<b>Heparin-associated thrombocytopenia.</b> Bo

intravascular coagulation. *Partial list.

hematous plaques on the forearm.

s with central crusts.

bullous pemphigoid; BSLE, the bullous eruption of systemic lupus erythematosus;

formation and an inflammatory infiltrate composed of neutrophils and eosinophils

32FT2.jpg|<b>Table 32.2</b>&nbsp;<b>Survey of controlled trials for the treatmen

Ronald Rapini, M.D.

41FF6.jpg|<b>Fig. 41.6</b>&nbsp;<b>Gustatory sweating in the auriculo-temporal (

howing a papular quality caused by rubbing.</b>

45FT1.jpg|<b>Table 45.1</b>&nbsp;<b>Major clinical and laboratory manifestations

47FF6.jpg|<b>Fig. 47.6</b>&nbsp;<b>Histopathology of scleromyxedema.</b> Typical

lossia with dental impression on the tongue.

50FF8.jpg|<b>Fig. 50.8</b>&nbsp;<b>Histologic features of porphyria cutanea tard

re is both hyperpigmentation and desquamation of the skin.

53FT9.jpg|<b>Table 53.9</b>&nbsp;<b>Associated cutaneous findings in Crohn&#8217

55FT4.jpg|<b>Table 55.4</b>&nbsp;<b>Hereditary epidermolysis bullosa (EB).</b>

59FF9.jpg|<b>Fig. 59.9</b>&nbsp;<b>Darier's disease.</b> Nail changes with longi

sen R, eds. Pediatric Dermatology. &#169; Churchill Livingstone, 1995.

F1, and so these patients would be considered &#8216;NF1 suspects&#8217;.

omplex.</b> For example, liver or spleen carcinomas.

63FF6.jpg|<b>Fig. 63.6</b>&nbsp;<b>Muir&#8211;Torre syndrome with multiple sebac

63FT6.jpg|<b>Table 63.6</b>&nbsp;<b>Cutaneous manifestations of mitochondrial re

64FF16.jpg|<b>Fig. 64.16</b>&nbsp;<b>&#8216;Milk lines&#8217;</b>. Supernumerary

n melanocytes.</b> Because the KIT receptor is a tyrosine kinase receptor, it ha

65FF12.jpg|<b>Fig. 65.12</b>&nbsp;<b>Causes of increased melanin production.</b>

Cutan Med Surg. 1997;16:3&#8211;14.

66FF24.jpg|<b>Fig. 66.24</b>&nbsp;<b>Onchocerciasis.</b> Depigmentation of the s

67FF9.jpg|<b>Fig. 67.9</b>&nbsp;<b>Linear postinflammatory hyperpigmentation.</b

+</sup>Most have block-like configuration; <sup>&#8225;</sup>Single case.

68FT1.jpg|<b>Table 68.1</b>&nbsp;<b>Complex functions of hair and nails.</b>

69FF16.jpg|<b>Fig. 69.16</b>&nbsp;<b>Trichorrhexis invaginata (bamboo hair).</b>

72FF6.jpg|<b>Fig. 72.6</b>&nbsp;<b>Traumatic ulcer.</b> This lesion of the later

73FF13.jpg|<b>Fig. 73.13</b>&nbsp;<b>Vulvar dermatitis.</b> Lichenification is p

74FF16.jpg|<b>Fig. 74.16</b>&nbsp;<b>Clinical manifestations of brucellosis.</b>

(type 2 reaction) with the appearance of multiple red papulonodules in a patien

75FT7.jpg|<b>Table 75.7</b>&nbsp;<b>Initial treatment of tuberculosis.</b> Modif

crumbling and thickening of the fingernails (<b>A</b>) and toenails (<b>B</b>).

sup>.</b> *Sexual reproduction.

78FF6.jpg|<b>Fig. 78.6</b>&nbsp;<b>Disseminated cryptococcosis in the setting of

79FF6.jpg|<b>Fig. 79.6</b>&nbsp;<b>Verrucae vulgares or common warts.</b> Courte

79FT2.jpg|<b>Table 79.2</b>&nbsp;<b>Management of anogenital warts with grading

rsity Press, 1994.

82FF22.jpg|<b>Fig. 82.22</b>&nbsp;<b>Worldwide distribution of donovanosis.</b>

tric Dermatology. 2nd edn. Vol. 2. Edinburgh: Churchill Livingstone, 1995:1347&#

0FF1.jpg|<b>Fig. I.1</b> <b>Macule.

9FF20.jpg|<b>Fig. 9.20</b> <b>Microabscess of Munro</b>. Remnants of neutro

12FF22.jpg|<b>Fig. 12.22</b> <b>Chronic sclerodermoid graft-versus-host dis

particularly in combination with IFNγ, promotes production of chemokines su

14FF2.jpg|<b>Fig. 14.2</b> <b>Adult seborrheic dermatitis of the face and s

15FF14.jpg|<b>Fig. 15.14</b> <b>Allergens being marked upon removal of Scan

17FF4.jpg|<b>Fig. 17.4</b> <b>Initial subclinical response to tissue pertur

18FT3.jpg|<b>Table 18.3</b> <b>The most common plants causing toxin-mediate

22FF7.jpg|<b>Fig. 22.7</b> <b><i>In vitro</b> inhibition of Fas-mediated ke

23FF14.jpg|<b>Fig. 23.14</b> <b>Heparin-associated thrombocytopenia.</b> Bo

32FT2.jpg|<b>Table 32.2</b> <b>Survey of controlled trials for the treatmen

41FF6.jpg|<b>Fig. 41.6</b> <b>Gustatory sweating in the auriculo-temporal (

45FT1.jpg|<b>Table 45.1</b> <b>Major clinical and laboratory manifestations

47FF6.jpg|<b>Fig. 47.6</b> <b>Histopathology of scleromyxedema.</b> Typical

50FF8.jpg|<b>Fig. 50.8</b> <b>Histologic features of porphyria cutanea tard

53FT9.jpg|<b>Table 53.9</b> <b>Associated cutaneous findings in Crohn&#8217

55FT4.jpg|<b>Table 55.4</b> <b>Hereditary epidermolysis bullosa (EB).</b>

59FF9.jpg|<b>Fig. 59.9</b> <b>Darier's disease.</b> Nail changes with longi

sen R, eds. Pediatric Dermatology. © Churchill Livingstone, 1995.

F1, and so these patients would be considered ‘NF1 suspects’.

63FF6.jpg|<b>Fig. 63.6</b> <b>Muir–Torre syndrome with multiple sebac

63FT6.jpg|<b>Table 63.6</b> <b>Cutaneous manifestations of mitochondrial re

64FF16.jpg|<b>Fig. 64.16</b> <b>‘Milk lines’</b>. Supernumerary

65FF12.jpg|<b>Fig. 65.12</b> <b>Causes of increased melanin production.</b>

Cutan Med Surg. 1997;16:3–14.

66FF24.jpg|<b>Fig. 66.24</b> <b>Onchocerciasis.</b> Depigmentation of the s

67FF9.jpg|<b>Fig. 67.9</b> <b>Linear postinflammatory hyperpigmentation.</b

+</sup>Most have block-like configuration; <sup>‡</sup>Single case.

68FT1.jpg|<b>Table 68.1</b> <b>Complex functions of hair and nails.</b>

69FF16.jpg|<b>Fig. 69.16</b> <b>Trichorrhexis invaginata (bamboo hair).</b>

72FF6.jpg|<b>Fig. 72.6</b> <b>Traumatic ulcer.</b> This lesion of the later

73FF13.jpg|<b>Fig. 73.13</b> <b>Vulvar dermatitis.</b> Lichenification is p

74FF16.jpg|<b>Fig. 74.16</b> <b>Clinical manifestations of brucellosis.</b>

75FT7.jpg|<b>Table 75.7</b> <b>Initial treatment of tuberculosis.</b> Modif

78FF6.jpg|<b>Fig. 78.6</b> <b>Disseminated cryptococcosis in the setting of

79FF6.jpg|<b>Fig. 79.6</b> <b>Verrucae vulgares or common warts.</b> Courte

79FT2.jpg|<b>Table 79.2</b> <b>Management of anogenital warts with grading

82FF22.jpg|<b>Fig. 82.22</b> <b>Worldwide distribution of donovanosis.</b>

87FF14.jpg|<b>Fig. 87.14</b> <b>Chronic actinic dermatitis</b>. Lichenified

90FF3.jpg|<b>Fig. 90.3</b> <b>Slap mark on the cheek.</b> Ecchymoses which

91FF15.jpg|<b>Fig. 91.15</b> <b>Cutaneous Rosai–Dorfman disease.</b>

97FF15.jpg|<b>Fig. 97.15</b> <b>Histology of lichen sclerosus.</b> Homogeni

+</sup>This classification has been replaced by ref. 5. <sup>‡</sup>The pr

100FF7.jpg|<b>Fig. 100.7</b> <b>Atrophoderma vermiculatum.</b> Multiple sma

ome (Wyburn–Mason's syndrome) involving the centrofacial skin, the retina

107FF3.jpg|<b>Fig. 107.3</b> <b>Livedo reticularis.</b> A mottled or net-li

115FF16.jpg|<b>Fig. 115.16</b> <b>Classic Kaposi's sarcoma.</b> Red macules

117FF9.jpg|<b>Fig. 117.9</b> <b>Differentiating dermatofibroma (DF) and der

118FF10.jpg|<b>Fig. 118.10</b> <b>Angiolipoma. A</b> In angiolipomas, matur

128FT24.jpg|<b>Table 128.24</b> <b>Dosing of amphotericin B.</b>

130FT1.jpg|<b>Table 130.1</b> <b>Cutaneous absorption by anatomic site.</b>

132FF2.jpg|<b>Fig. 132.2</b> <b>P-Glycoprotein.</b> This is an ATP-dependen

134FF6.jpg|<b>Fig. 134.6</b> <b>Emission spectrum of a typical UVA-1 light

137FF2.jpg|<b>Fig. 137.2</b> <b>Superficial hemangioma. A</b> Before treatm

140FF4.jpg|<b>Fig. 140.4</b> <b>Bipolar forceps attached to an electrosurgi

143FT2.jpg|<b>Table 143.2</b> <b>Differential diagnosis of local anesthetic

147FF10.jpg|<b>Fig. 147.10</b> <b>Single tangent advancement flap. A</b> La

148FF8.jpg|<b>Fig. 148.8</b> <b>Harvesting and placement of a free cartilag

151FF10.jpg|<b>Fig. 151.10</b> <b>Wound infection and necrosis at full-thic

155FF9.jpg|<b>Fig. 155.9</b> <b>Complications from Baker's phenol peel.</b>

158FF3.jpg|<b>Fig. 158.3</b> <b>Androgenetic alopecia.</b>